Questionnaire

Summary of the main activities of a scientific Organisation

of the Slovak Academy of Sciences

Period: January 1, 2003 - December 31, 2006

I. Formal information on the assessed Organisation:

1. Legal name and address

Institute of Experimental Endocrinology, SAS

Vlárska 3

833 06 Bratislava

2. Executive body of the Organisation and its composition

Directoriat name age years in the position

director MUDr. Vladimír Štrbák, DrSc. 63 2003

deputy director Ing. Štefan Zorad, CSc. 50 2003

scientific secretary

Prof. PharmDr. Daniela Ježová, DrSc.Prof. MUDr. Iwar Klimeš, DrSc.Ing. Július Brtko, DrSc.

55 1995

Head of the Scientific Board

Prof. MUDr. Iwar Klimeš, DrSc.

3. Basic information about the research personnel

i. Number of employees with a university degree (PhD students excluded)

engaged in research and development and their full time equivalent work

capacity (FTE) and average number during the assessment period in

2003 = 39 (36,75), 2004 = 39 (37,28), 2005 = 40 (37,63), 2006 = 39 (36,89)

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ii. Organisation units/departments and their FTE employees with the university

degree engaged in research and development

No. FTE No. FTE No. FTE No. FTE No. FTE

organisation in whole 39 36,75 39 37,28 40 37,63 39 36,89 39,25 37,14

Laboratory of Human Endocrinology 4 4 4 4 3 3 3 3 3,5 3,5

Laboratory of Molecular Endocrinology

6 5,25 4 3,35 5 4,25 5 4,25 5 4,275

Laboratory of Pharmacological Neuroendocrinology

5 5 5 5 4 4 4 4 4,5 4,5

Laboratory of Stress Research 8 6,5 7 6,35 6 6 5 5 6,5 5,963

Laboratory of Diabetes and Nutrition 5 5 6 6 7 7 6 6 6 6

Laboratory of Developmental Genetics

2 2 3 3 4 4 4 4 3,25 3,25

Laboratory of Neurohumoral Regulations

4 4 2 2 2 2 2 2 2,5 2,5

Laboratory of Metabolic Regulation 5 5 8 7,68 7 5,38 4 3,14 6 5,3

Laboratory of Functional Neuromorphology

0 0 2 2 3 2,5 1,25 2,25

Laboratory of Cell Endocrinology 0 0 0 3 3 0,75 3

Research staff2003 average200620052004

4. Basic information on the funding

i. Total salary budget1 of the Organisation allocated from the institutional

resources of the Slovak Academy of Sciences (SAS) in 2003, 2004, 2005, 2006,

and average amount for the assessment period

Salary budget 2003 2004 2005 2006 average

total salary budget (millions of SKK) 13,353 13,740 14,703 15,750 14,387

5. URL of the Organisation’s web site

www.endo.sav.ak

1 Sum of the brutto salaries without the fund contributions.

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II. General information on the research and development activity of

the Organisation:

1. Mission Statement of the Organisation as presented in its Foundation

Charter

The Institute of Experimental Endocrinology of the Slovak Academy of Sciences is focused on the basic research of neuroendocrine regulation systems with the aim to clarify their roles in regulation of different physiological functions of an organism using model situations including development, loading and in relation to etiopathogenesis of various diseases.

Institute performs studies of mechanisms of hormone effects and their role in metabolism, aging, nutrition, tissue regeneration and development of major diseases.

Institute elaborates new investigative methods of endocrine system for helping to solve problems in detection of endocrine system disorders.

Institute provides consulting and expertise services in accordance with its main activities.

Institute is pursuing scientific education in accordance with valid legislation.

Results of scientific activities are published in relevant periodic and non periodic press.

2. Summary of R&D activity pursued by the Organisation during the assessed

period, from both national and international aspects and its incorporation in

the European Research Area (max. 10 pages)

Introduction:

The scientific research activities of the Institute over the last four years have continually followed up the existing main research focuses in the area of endocrinology and metabolism. They have been performed in harmony with the most progressive trends and accent at investigations of molecular mechanisms of the genesis, development and innovative diagnostics of non-infectious civilization diseases. In agreement with Mission Statement presented in the Foundation Charter of the Institute a special attention has been paid to two directions, in particular to

a) The neuroendocrine regulation of body functions with special emphasis on the elucidation of processes operating in stress situations and their significance for the cardiovascular and immune systems, or physiology and/or pathology of brain functions and mental states

b) Studies of biological action of hormones, cytokines and other bioactive molecules of endo- or exogenous origin at the DNA, RNA and protein level during their influencing of metabolic processes in the cells, both the in vitro situation and/or under conditions of integrated organism with the aim to identify the principle diseases mechanisms or to improve and innovate diagnostics and treatment of selected diseases

A significant part of the research capacity of the Institute has been concentrated on the role of the endocrine system in the development and progression of socially important diseases as obesity and the metabolic syndrome, type 2 diabetes, cardiovascular and rheumatoid diseases, or mental impairments.

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Five research projects of the 5th Framework Program of the European Commission were successfully concluded within the evaluated period. This concerns particularly the investigations on the role of retinoic acid in regulation of gene expression in relation to the processes of biological aging /acronym VITAGE; 2000-03/ and the project on evaluating the effect of environmental pollution with endocrine disruptors on the health status of the populations of selected areas of East Slovakia /acronym PCBRISK; 2001-04/. The latter project won also the Slovak Academy of Sciences Award for “Excellent research data achieved in collaboration with the Safarik University and the Slovak Health University”.

A special project of the 5th FP, STRESSNUTS /2000-04/ had also concluded within the evaluated period. The project dealt with reduction of negative impact of environmental factors on human health and was the base for granting our Institute with the status of a „Centre of Excellence“supported financially by the European Commission. The main achievements of the project, which was a collective endeavour of the core Laboratories of the Institute and their international collaborations, included generation of important scientific data with relevance to clinical research.

In particular, evidence has been obtained to support further research on several molecules known to modulate hormone release and potentially interesting for treatment of the negative impact of stress, anxiety and depression (e.g. felbamate, phenytoin, lamotrigin, citalopram, tianeptine, Ginco biloba extracts or pentoxifylline). Also, new mechanisms involved in the stress response have been revealed; e.g. the findings on gene expression of adrenaline synthesizing enzyme in cardiac tissue in normal and corticoliberin gene deficient mice. The results contributed to understanding of regulation of the heart function by glucocorticoids, or the proof for a direct biosynthesis of adrenaline in the sympathetic ganglia which might clarify the mechanism of signal transmission at the ganglionic level. The original data on evaluation of the non-verbal behaviour during stress exposure and its modulation by drug treatment etc. were obtained.

Important data were gathered in the field of nutritional manipulations and metabolic research; e.g. whole body insulin sensitivity and glucose utilization depends on fatty acid composition of the diet, where dietary fat rich in long chain saturated fatty acids led to insulin resistance, meanwhile feeding the medium chain triglyceride prevented the high fat diet-induced decrease of insulin action. Studies on mechanism of leptin action have underlined its important role in the regulation of fuel sensing mechanism in health and obesity. It was also shown that dietary supplementation of specific amino acids can be recommended for prevention of stress-related anxiety disorders.

Funding of the STRESSNUTS project enabled further increase in the quality of the scientific research at our Institute, to become an international center for training of doctoral students and post-doctoral fellows from EU countries, and also to organize three important international scientific symposia attended by the top researchers from the field.

Further two research grants from the 5th FP of the EC dealt also with very interesting themes. The goal of ENDOMET project (2003-2006) was to determine whether plasticisers, which are widespread environmental contaminants, could affect only the human reproductive system or also human neuronal and thyroid development and function and which mechanisms might be involved. Within the basic research, a successful application into the 5th FP encompassed a project devoted to a construction of novel collection of chromosomal applications in drosophila melanogaster /acronym DROSDEL; 2003-04/. The latter studies, partly originated also from data gained within a NATO supported project, which had been devoted to genes controlling the apoptosis during the metamorphosis of drosophila.

Also within the 6th FP of the EC, the Institute had two successful grant applications, i.e. one on the role of chemical contaminants in the food chain /acronym CASCADE; 2004-09 / and the Danubian Biobank Initiative: Towards Information Based Medicine (acronym DANUBIOBANK; 2006-07).

The above mentioned projects of the European Commission in Brussels, and particularly several grants from the Science and Technology Assistance Agency /APVT/ or from the Agency for Support of Science and Research /APVV/ as well as the state program Cardiogenomics, the grants from the Scientific Grant Agency /VEGA/, the Slovak Ministry of Health, the Slovak Ministry of Education, the European Social Fund/ enabled in the accredited period a significant innovation of the methodological approaches used at our Institute, even establishment and progressive development of new workplaces within our Institute.

In 2003, the Diabetes and Nutrition Laboratory of the Institute established in collaboration with the National Institute of Endocrinology and Diabetes in Lubochna, the DIABGENE laboratory, a joined workplace residing at our Institute in Bratislava. Its mission has been the screening and DNA diagnostics of monogenic forms of diabetes in the Slovak Republic. Since 2004, the DIABGENE has been participating in endeavors of an

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international team which has led in 2006 to discovery of a genuinely new, pharmacogenomics-based treatment of permanent neonatal diabetes.

In 2005, a second joined laboratory – the MicroPET Laboratory - was established at this Institute due to cooperation between the BIONT Company and our Institute. The aim of this laboratory is to carry out the positron emission tomography in small laboratory animals.

In terms of analytical equipment availability at the Institute, the aforementioned domestic and foreign research grants have allowed a significant progress when compared to the previous accredited period. Regarding larger investments, beside of the miniPET apparatus, the DIABGENE Laboratory succeeded to acquire a second capillary automatic sequencer, which in combination with a recently purchased dHPLC apparatus enabled creation of a high throughput sequencing center.

In agreement with the aims of the research strategy presented at the previous evaluation period, intensive efforts have been launched with the aim to strengthen the international collaboration on base of joined projects, for which financing from the research grant agencies had been obtained, particularly from the European Commission. The international collaboration is a considerable factor, traditionally contributing to an adequate publication and citation activity of our Institute. Moreover, the latter is keeping a moderately increasing trend also in this evaluation period.

2. A. THE RESEARCH STATUS AND A BRIEF CHARACTERISTICS OF RESULTS ACHIEVED

WITHIN THE EVALUATED PERIOD

2. A.1. The most remarkable results obtained

- Mutations in the KCNJ11 and ABCC8 genes encoding the Kir6.2 and SUR1 subunits of the pancreatic B cell KATP channel have recently been shown to be the most common cause of permanent neonatal diabetes (PNDM). Information regarding the frequency of PNDM has been based mainly on non-population or short-term collections only. Therefore, using the unique Slovak Children Diabetes Registry eight patients with diabetes fitting the PNDM definition (i.e. diabetes onset before the 6 th month of life without remission) were identified and for the first time a true, diabetes registry based PNDM incidence was calculated. In Slovakia, it is much higher /1: 215,417 live births/ than international estimates /1: 800,000/ shown elsewhere. In four patients, 3 different Kir6.2 mutations were found (two cases with R201H, and two novel mutations H46Y and L164P). Three patients with the Kir6.2 mutations R201H and H46Y were transferred from insulin to sulphonylurea, decreasing their HbA1c from 9.3-11.0% on insulin to 5.7-6.6% on sulphonylurea (SU) treatment. One patient has a novel V86A mutation in the SUR1 gene, and was also successfully transferred to SU. The results obtained are an excellent example of the translational approach in medicine, and the very first classical example of pharmacogenomics in diabetology, since the genetic cause of the insulin deficiency determines the response to treatment. The data has been published also in the prestigious NEJM with the top third impact factor in biomedicine at all (I. Klimeš)

- It was shown that cell swelling (e.g. induced by hypotonicity) induces insulin secretion exploiting novel signaling pathway different of that involved in the glucose-induced insulin release. Cell swelling-induced exocytosis possesses specific features. This mechanism is relatively unspecific, thus advantage can be taken when studying control of peptides secretion in localization where their role is unknown (e.g. TRH in heart). It is supposed that signaling steps of swelling-induced secretion may soon become a drug target for molecules affecting secretion of many proteins and peptides. This might be of special interest for regulation of insulin secretion both for research and/or therapeutic purposes (V. Štrbák)

- Using a model of psychosocial stress, it was shown /in contrast to traditional believes/ that secretion of stress hormones in persons with high trait anxiety may be rather low, and that increased levels of hormones during stress situations contribute to better coping with stress. Consistent with the traditional view, the rise in heart rate during stress was higher in anxious subjects than in non-anxious ones. However, plasma levels of cortisol, adrenaline and noradrenalin during stress were lower in anxious subjects. It was also shown that subjects with better cognitive performance in another model of mental stress had significantly higher cortisol levels compared to persons with worse performance. Correlation analysis in anxious subjects showed that lower ACTH and cortisol stress responses were associated with exaggerated perception of stress and depression feelings. The data obtained suggest that an adequate concentration of cortisol is needed for optimal emotional and cognitive coping with stress (D. Ježová)

- It seems that imbalance between immuno-stimulating and immuno-suppressive hormones may predispose to development of rheumatic disorders. Therefore, hormone levels were analyzed in the synovial fluid of patients with rheumatoid arthritis (RA) and in patients with osteoarthritis (OA). Testosterone and estradiol levels were

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lower, and aldosterone, insulin and C-peptide levels were higher in the synovial fluid than in plasma. Overall levels of proinflammatory hormones were higher in synovial fluid of the RA patients. Low levels of dehydroepiandrosterone, the precursor of active androgens and estrogens, were confirmed in females with premenopausal onset of RA. Elevated plasma PRL levels were observed in about one third of patients with RA and Systemic Lupus erythematosus (SLE). Increased frequency of glucocorticoid treatment in hyperprolactinemic RA patients compared to normoprolactinemic suggested that the imbalance between glucocorticoids and PRL might play an aggravating role in RA. Taken together, the data supports the introduction of dehydroepiandrosterone supplementation in therapy of RA (L. Macho)

- Obesity due to high caloric intake or due to growth hormone deficiency (GHD) may result in subclinical proinflammatory situation. Thus, molecular mechanisms of both situations were studied. The mRNA levels for CD68 and CD14 (markers of macrophage activity) and proinflammatory adipokines (TNFalpha, IL-6, PAI-1) were higher in fasting state or during euglycemic hyperinsulinemia. Gene expression for proinflammatory parameters showed a continual increase over a range of the s.c. adipose tissue (AT) mass, both in obesity and GHD. Inflammation in AT of obese subjects was analyzed using a high-throughput protein cytokine assay showing 27 proteins presented at higher levels. Among them were leptin, growth factors and their receptors, number of chemokines, cytokines and their receptors, and other receptors and enzymes. Selected protein array results were verified using the real-time PCR. This is the first evidence on „molecular disease” mechanisms of chronic inflammation in AT of clinically yet healthy obese young men. Chronic inflammation is present also in GHD, where accumulation of central AT together with an insufficient insulin secretion during oGTT seem to contribute to impaired glucose tolerance seen in the GHD subjects (D. Gašperíková)

- Elaboration of experimental models of disease states resulted into new information on the mechanisms involved in development of depression and addictive behaviour. Gender dependent differences of gene expression in selected brain regions of a rat model of experimental depression seem to support the gender differences in incidence of depressive disorders in man. Anhedonic animals also exhibited depression-like symptoms, e. g. increased basal and decreased stress-induced hormone levels, increased gene expression for corticoliberin (CRH) in the hypothalamus and selective changes in glutamate receptor subunit gene expression in regions of brain reward system. The aforementioned indicates a role of CRH and glutamate in pathogenesis of depression. 3 weeks of voluntary wheel running by the Lewis rats resulted in development of compulsive running for 4-6 km/day. In this model of non-substance addiction, the most significant changes were observed in stress hormones and glutamate receptor gene expression in the brain. Changes observed might be important for development of the addictive behaviour as pharmacological blockade of glutamate release by phenytoin prevented development of compulsive running (D. Ježová)

- High prevalence of disorders of the reproductive system in Europe seems to be in part result of environmental contamination by endocrine disruptors. This is a very diverse group of chemicals intensively used as a plasticizers, cosmetic ingredients, pharmaceuticals and pesticides. Effects of selected environmental plasticizers were studied in primary cell culture system of granulosa cells isolated from porcine ovarian pre-ovulatory follicles. The results indicated that the tested phenol and phthalate derivatives could induce changes in basal as well gonadotropin-stimulated progesterone and estradiol production by granulosa cells. Marked changes were observed by the action of bisphenol A, chlormethyl phenol, benzylbutyl phthalate and di (2-ethylhexyl) phthalate. We suppose that environmental plasticizers may act at the level of enzymes involved in steroid genesis in follicular cells as well as interfere with signal pathways of gonadotropin action in steroid hormone production. The inhibitory action of phenols on oocyte nuclear maturation and hyaluronic acid retention in the oocyte-cumulus complex matrix suggests ability of these compounds to influence the processes required for successful ovulation and fertilization (M. Ficková)

- The age related alterations in the gene regulating abilities of retinoic acid, the biologically active form of vitamin A were investigated. Its counterparts, nuclear retinoic acid receptors belong to a superfamily of the retinoid-inducible transcription factors. Our data has shown for the first time that human lymphocytes express - besides the known two subtypes of all-trans retinoic receptor RAR alpha, RAR gamma, and the known one subtype of 9-cis retinoic acid receptor RXR alpha - also the second 9-cis retinoic acid receptor, RXR beta. The data has shown that RXR beta receptor expression is significantly decreased in lymphocytes in a group of old men when compared to that of young men. We have shown also for the first time the rate of distribution of retinoic acid receptor subtype expression in human lymphocytes from young men who are in the following order: RXR beta (39.8 %), › RAR gamma (32.4 %), and › RXR alpha (17.8 %), › RAR alpha (10.3 %). Supplementation with 13-cis retinoic acid changes the distribution pattern predominantly of retinoid X beta receptor expression in human lymphocytes: RXR beta (34.2), › RAR gamma (35.9 %), and › RXR alpha (20.1 %), › RAR alpha (9.8). Decreased RXR beta expression may indicate toward higher risk of altered immune function in healthy elderly subjects. Consequently, retinoic acid supplementation might be beneficial in prevention of the immune dysfunction (J. Brtko)

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- By studying hormone-triggered programmed cell death (PCD) in larval salivary glands during metamorphosis of Drosophila we have identified a series of genes (P58IPK, Hsc70.3, Ca-P60A, Crc, Cnx99A, Cct5 and Hop) responsible for immediate activation of execution phase of the apoptosis which takes place by disintegrating endoplasmic reticulum (ER) into vesiculated lamellae. Within rapidly forming ER vesicles we have found increased abundance of myelin-like structures that are typical for accumulation of incorrectly folded proteins indicating lowered function of ER chaperones. This suggests that Drosophila salivary gland PCD reflects accumulated ER stress as a result of the unfolded protein response (UPR). The inappropriate UPR signaling is often associated with several degenerative diseases including Parkinson’s, Huntington’s, Alzheimer, Lou-Gehrig disease or amyotrophic lateral sclerosis (ALS) the common feature of which is formation of inclusions inside of ER lumen. Identification of novel components of signaling pathways that take part in the control of cell transformation, hormonal response and apoptosis can provide new therapeutic or diagnostic vistas at much higher efficiency if we use well-defined model system such as Drosophila (R. Farkaš)

2. B. SPECIFIC RESULTS IN INDIVIDUAL RESEARCH AREAS

2. B.1. In elucidation of the role of neuroendocrine regulation of body functions with special emphasis upon the knowledge on stress situations

- Measurements of gene expression for enzymes responsible for synthesis of adrenaline and noradrenalin in the heart of rat have shown a gene expression for PNMT which is responsible for the adrenaline synthesis; meanwhile gene expression for the tyrosine hydroxylase was not detected. The data has shown that PNMT mRNA is not localized in the neural cells of the heart as has been anticipated; instead it is present within the cardiomyocytes where it responds by an increase of PNMT gene expression to stress. Gene expression for PNMT was detected also in human heart and we hypothesize that changes in the gene expression may play an important role for example in regulatory processes following heart transplantation (R. Kvetňanský).- During studies aimed on regulation of gene expression for enzymes of the catecholaminergic system and their modulation by transcription factors in mammals during stress, it was found that both the tyrosine hydroxylase (TH) activity and the gene expression for TH of cold adapted rats did not differ from the control animals. However, in the repeatedly immobilized rats remained those parameters highly increased. The substance for the differences found is the probably the impaired activation of the transcription factors Fra-2, phosphorylated CREB and Egr-1. The results indicate that absence of those transcription factors may cause the adaptation of the TH expression in response to coldness (R. Kvetňanský).- Investigations after short- and long-term stress have shown in the adrenal gland cortex of CRH „knockout“ mice (which are not capable to synthesize a functional neuropeptide corticoliberin axis) a substantial reduction of gene expression for and protein levels of the fenylethanolamine-N-methyltransferase (PNMT) when compared to the „wild-type“ animals. Our findings confirm the crucial role of glucocorticoids for a normal production and function of the PNMT in stress (R. Kvetňanský).

- Effect of acute peripheral administration of Zolpidem (a GABAA receptor agonist with selectivity for α1

subunits) was studied on functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei using dual Fos/OXY immunohistochemistry. The data of this study provide insight into the topographic patterns of brain activity within the clusters of magnocellular OXY cells in the hypothalamus. They indicate that stimulation of GABAA benzodiazepine receptors activates not only the stress responsive CRH neurons, but also the OXY neurons located in PVN and ACC, and not in SON. We showed that the regulatory role of this GABAA receptor is wide-ranging and different even within the functionally very similar magnocellular population of OXY neurons in the hypothalamus (A. Kiss).

- The role of central alpha2-adrenoceptors in the regulation of hypothalamic magnocellular cells was studied under treatment with alpha2-adrenoceptor agonist, xylazine (XYL) and compared with effects of hyperosmotic challenges induced by hypertonic saline (HS). It was found that the peripheral administration of XYL is a potent stimulus for oxytocinergic (OXY), but not vasopressinergic (AVP) population of magnocellular cells eliciting a marked activation (Fos expression) in discrete population of OXY neurons in both the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. It was also found that higher osmotic challenge entirely overlaps the effect of XYL. Moreover, XYL pretreatment considerably reduces the activity of the CRH-producing parvocellular population of PVN cells activated by higher concentrations of HS. These data indicate for the first time that alpha2-adrenoceptors have broader impact in the regulation of hypothalamic neurons as assumed so far (A. Kiss).

- Studies aimed at traditional and unconventional mechanisms of regulation of peptide secretion have proven gene expression for TRH in the rat heart. The gene expression is raised two fold in the left auricle when compared top the left ventricle. TRH secretion by slices of both the auricle and ventricle in vitro displays attributes of regulated secretion: it can be stimulated by hypoosmosis (i.e. by cell swelling) as well as by a depolarization of the plasma membrane using KCl. TRH secretion can be inhibited by angiotensin II, where this action is mediated via the AT1 receptors. TRH seems to be a part of a system determining some functions of the cardiovascular apparatus. Moreover, also the expression of the prepro-TRH in heart was proven, which

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significantly increases in transgenic rats with an extra gene for renin. TRH is more intensely produced and expressed in the atrium than in the ventricle. The cell swelling-induced secretion can be unmasked also in specifically (i.e. reversely) responding cells which are engaged in regulation of the water and electrolyte metabolism. This can take place by inhibiting a specific response – via mechanosensitive receptors activated channels with aid of the GdCl3 (V. Štrbák).

- Within the project aimed at evaluation of neuroendocrine mechanisms in relation to mental state and the effects of psychotropic drugs, using the model of long-term voluntary wheel running of rats (which has a compulsory character), the possible role of the stress hormone oxytocin, which has been anticipated to participate in regulation of some cardiovascular functions, was studied. It was found in the running rats that the oxytocin concentration decreases in neurohypophysis without a parallel change of its plasma levels. Voluntary running led however to a decrease of oxytocin content in the heart auricle, which indicates to a possible role of oxytocin during a long term physical activity coupled with compulsive behavior (D. Ježová).

- Proofs about a modulatory effect of the antiepileptic drug lamotrigine on the hormonal and cardiovascular response to mental stress were obtained in healthy volunteers. Lamotrigine has an inhibitory effect on the glutamatergic neurotransmission and the data obtained represent the first, although an indirect proof of the role of endogenous excitatory amino acids during stress in man. The results brought also the first information about changes of the non-verbal behaviour during psychosocial stress in response to endocrine changes. The effect of lamotrigine on hormone secretion plays probably an important role during its thymoprophylactic action in treatment of the bipolar disorder (D. Ježová).

- During assessment of the importance of changes of neuroendocrine mechanisms at the origin of hypertension and insulin resistance in young, non-obese males with newly-diagnosed and yet untreated hypertension of the 1. grade and/or with high normal blood pressure, no changes in plasma adrenaline, noradrenalin, cortisol, PRA and aldosterone were found in response to a metabolic stress stimulus (i.e. to insulin-induced hypoglycemia). The hypertensive subjects had, however, a lower response of the somatotrophic and lactotrophic axis to hypoglycemia. Interestingly, the hypoglycemia nadir was in spite of the insulin resistance in the hypertensive subjects in both groups identical. The cause for the aforementioned could be located at the level of central mechanisms of the contraregulatory response. In particular, based upon the decreased response to the alpha2-adrenergic stimulation with clonidine, it was hypothesized that the decrease of growth hormone and prolactin response to hypoglycemia is given by a defect at the level of the alpha-adrenergic receptors at the hypophyseotrophic neurons (M. Vigaš).

2. B.2. In the area of studies on the biological action of hormone, cytokine and other bioactive molecules of endo-or exogenous origin at the DNA, RNA and   protein level for

2. B.2.1. Influencing of metabolic processes

- Studies on elucidation of the role of the local renin-angiotensin systems in adipose tissue, spleen, lymphocytes and carcinoma of the mammary gland have shown that losartan administration, a blocker of the AT1 receptors, to rats led to the known effect of increasing the gene expression for renin in the kidney cortex with a subsequent enormous increase of plasma rennin activity /PRA/. Furthermore, raised renin kidney activity (KRA) after losartan administration was found both in the kidney cortex and the medulla, respectively. It is proposed that the increase of KRA and PRA arises due to the raised renin expression in the kidney cortex as a consequence of lower levels of the cytoplasmic calcium as induced by inhibition of the angiotensin II. action. Renin expression was noted also in the kidney medulla although it did not increase after losartan administration. This is the first report on this type of losartan action (Š. Zórad).

- During studies on monitoring the effect of 13-cis retinoic acid (a differentiation-inducing agent) administration on adipose tissue parameters, gene expression for the components for the renin-angiotensin system /RAS/ and for the adipokines, a significant increase of the gene expression of the aP2 (fatty acid binding protein) marker was noted. This confirmed the raised adipocyte differentiation after administration of the retinoic acid. The increased transformation of preadipocytes into adipocytes became manifested also via the increased gene expression for the angiotensin AT1 receptors, and by the increased content of leptin and adiponectin in the adipose tissue.  Due to the production of new small fat cells significantly increased also the gene expression for markers of insulin sensitivity /GLUT 4 and PPARγ/. It is suggested that 13-cis retinoic acid induces the conversion of preadipocytes into adipocytes by creating heterodimers of the retinoic nuclear receptors with PPARγ (Š. Zorad).

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- Data on the importance of the transmembraneous /TM/ segment of membrane receptors in the mechanism of their activation have shown in A431 cell line that inhibition could be induced by: a) incorporation of TM into plasma membranes and b) by rigidisation of plasma membranes as induced by modification of the lipid composition. Decreased autophosphorylation of the EGF receptor was followed by inhibited phosphorylation of intracellular signaling proteins, what may significantly influence the terminal effect at the level of DNA replication, cellular proliferation and differentiation. The importance of these results relate to malignant cells over expressing EGF receptors (M. Ficková).

- In studies focused at development of experimental arthritis in rats under various nutritional conditions, levels of leptin, ACTH, corticosterone, IL-1beta and production of NO on the 10th and the 22nd day of adjuvant arthritis of male rats were measured in order to assess the regulatory relationship of leptin and its modulators during the early and late phase of experimental inflammation. Circulating leptin levels were significantly decreased already on the 10th day of the diseases similarly as its mRNA in the epididymal fat. The IL-1beta concentration, which is an activator of leptin production, was increased in the spleen already on the 10 th day. A significant activation of the HPA axis took place in the chronic disease phase. NO production was significantly raised in both intervals monitored. These results point to a dysregulation of leptin during adjuvant arthritis (J. Jurčovičová). - During investigations of molecular mechanisms, which participate in raised fatty acid oxidation v liver and skeletal muscle of rat as induced by leptin administration, it was found that a  single application leads to higher levels of triglycerides, fatty acids and glycerol in circulation with a parallel decrease in triglyceride concentrations in both tissues. The aforementioned effects associate with a higher fatty acid beta-oxidation in both tissues, though with different kinetics for the liver and muscle. Measurements of activities and gene expressions for key enzymes of mitochondrial and peroxisomal oxidation of fatty acids have shown that leptin stimulates oxidation particularly in the peroxisomes (E. Šeböková).

- Monitoring the effect of transfection of DNA vaccines in vivo in relation to the biological action of retinoic acids in normal and neoplastic tissue of the mammary gland, the effect of the 13-cis retinoic acid and the effect of CpG sequence containing oligodeoxynucleotides on the gene expression profile in spleen and in malign tumours of the mammary gland of the Sprague-Dawley rats, were studied using the cDNA macro array. The effect of the aforementioned components, whether independently or in combination, has induced both in the spleen and in the tumours of the mammary gland important changes in expression of more than 200 genes, which have not been described as yet (J. Brtko).

- Molecular-genetic studies of function and expression of the hormone responsive dehydrogenase in Drosophila melanogaster have disclosed with aid of the analysis of the transcription units for the individual malate dehydrogenase (MDH) genes, that the transcription unit MDH53C1 codes for the synthesis of 4 and the MDH53C2 gene of 2 mRNA, whereby the two longest MDH53C1 transcripts reach by their second half of their 3‘-terminus into the transcription unit of the MDH53C2 gene. Both the 4 MDH53C1 mRNA and the 2 MDH53C2 mRNA originate via alternative splicing of different exons assuring identical N-terminal and middle areas, and different C-terminal ends of the MDH53C proteins. In contrast, the gene MDH87D1 for the cytosolic malate dehydrogenase codes production of only 2 mRNA using 2 independent promoters securing this was the origin of two isoforms of the MDH87D1 proteins, which differ in the N-terminal area and share identical C-terminal domains (R. Farkaš).

- The Juvenile hormone, similar to retinoids and thyroid hormones, as the last orphan ligand in animal kingdom plays a crucial role in regulation of cell differentiation and morphogenesis of Drosophila. Therefore, we have cloned and fully sequenced whole genomic region of the Met gene, residing on X chromosome and encoding bHLH-PAS protein homologous to dioxin receptors. Analysis of 13 Met alleles generated by radiation and P-element mutagenesis revealed unexpected complexity of MET protein action and provided groundwork for understanding Met- phenotypes including animal's resistance to JH. By combining pharmacological and genetic approaches we were able to disclose major pathway of JH cellular mode of action which involves Broad-Complex (BR-C) BTB/POZ transcription factor signaling by influencing timing of its action in context with ecdysone cascade. These observations have been confirmed by genetic interaction using double heterozygote crosses as well as by protein-protein interaction studies in yeast two-hybrid system (R. Farkaš).

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2. B.2.2 innovative diagnostics and treatment of selected diseases

-  With help of the National Diabetes Program (NDP), in 2003 the activities of the joined DIABGENE laboratory, which has been established under the patronage of the IEE SAS and of the National Institute for Endocrinology and Diabetes in Lubochna, were launched. The DIABGENE Laboratory as such resides at the IEE SAS in Bratislava. The Laboratory became over the three years step by step equipped with relevant hardware comparable with international standards (2 automatic sequencers, 1 dHPLC, 2 gradient PCR thermocyclers etc.), the DNA repository for monogenic diabetes was established and techniques for routine sequencing of the most common forms of the MODY diabetes and the real-time PCR diagnostics of the mitochondrial diabetes were set up. Moreover, mutation pre-screening using the dHPLC apparatus has been initiated. Based upon the DNA diagnostics of MODY diabetes subtypes clinical diabetologists in Slovakia are more and more utilizing the DNA results for introduction of „to the person tailored treatment“ plans /e.g. return from insulin to sulfonylurea in suitable cases of MODY 3 or the use of the diet treatment in the MODY2/. In collaboration with the Exeter University in UK, the diagnostic spectrum covers also the DNA diagnostics of various forms of the neonatal diabetes mellitus. Beside routine diagnostics of MODY subtypes within the territory of Slovakia, a couple of so far unknown mutations of permanent or transient neonatal diabetes have been discovered. These are now being investigated in terms of structure-function studies at the University of Oxford, UK. In addition, very important original results were achieved in respect to treatment of permanent neonatal diabetes producing the first pharmacogenomics data for practical use in clinical diabetology (I. Klimeš).

- Evaluations of the health risk due to a long-term exposition to low dose of polychlorinated biphenyls (PCB) have discovered that a significant contamination of the environment as documented with 4-times higher PCB serum levels of 1010 adults form the contaminated adults in comparison to 1040 subjects from non-contaminated counties was associated with increased volume of the thyroid gland, higher levels of thyroidal hormones (free thyroxin and total triiodothyronine) and with raised appearance of low levels of TSH in the zone of subclinical and manifest hyperthyroidism. This points to the role of PCB in the origin of an increased thyroid gland function as based upon displacement of thyroxin from its binding to protein carriers, and to a consequent increase of its turnover in the periphery (P. Langer)

- Moreover, significant correlations between the environmental pollution and the appearance of impaired glucose metabolism were found in 2047 subjects from a population chronically exposed to increased concentration of several organochlorine compounds. Their concentrations in circulation of the exposed persons correlated highly significantly with each other, which indicate to presence of a polycontamination. Associations between them depend upon the age and BMI, which are though simultaneously risk factors for diabetes and dysglycemia. With help of mathematical models for estimation of indices of insulin sensitivity (R HOMA, ISI McAuley, ISI Matsuda, ISI Cederholm) a higher frequency of insulin resistance in inhabitants of the contaminated areas was found what is in close harmony with a clearly higher appearance of diabetes and prediabetes in individuals with proven contamination by organochlorines (I. Klimeš)

- During studies of interaction of central and local hormonal and immunologic factors in pathogenesis and course of rheumatoid arthritis it was proven that the relatively modest hypocortisolemia in these patients was not caused by a decreased hypothalamic-hypophyseal regulation, but rather by a change in biosynthesis of corticoids in the adrenal cortex. Moreover, an isolated decrease in basal production of androgens (dihydroepiandrostendione sulphate, DHEAS), which have an important immunomodulatory action, is also taking place. An interesting finding was also a substantial lowering of the sympathetic adrenomedullary response to hypoglycemia, which may show up also during common stress situations in patients and alter regulation of immunity. The results point to an increase of the sulphotransferase activity in biosynthesis of corticoids and its contribution to a normal cortisol production (R. Imrich).

- Within the retinoic acid research project, further interesting data were achieved. In particular, using the Real-Time PCR original results on the expression of all subtypes of retinoic receptors (RARalpha, RARbeta RARgama) and rexinoid receptors (RXRalpha, RXRbeta a RXRgama) in an extremely malignant and rare tumor (Triton tumor) of child patient were obtained. Moreover, also a standard protocol was prepared for the diagnostics of retinoid receptors in malignant tumours of the human thyroid gland and mammary gland, which should enable to make an estimate of the success rate of treatment with retinoic acid derivatives in clinical cases (J. Brtko).

- Evaluations of the relation structure-function of insulin analogues as prepared by modification of the C-terminus from the B-chain of insulin included also testing of a series of insulin analogues derived from the des-tetrapeptide (B27 – B30) of insulin. These were modified via the N-methylation of the peptide binding in the B23 – B24 position and also by exchanging of aminoacids in positions B25 or B26. Measuring the ability of the analogues to stimulate glucose transport into the rat adipocytes and binding to the receptor of the adipocyte membranes, it was found that the substitution TyrB26 with histidine has a positive influence on the biological activity of the peptide. N-methylation of the peptide bond B23 – B24 and B24 – B25 has a negative impact on

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the analogue potency. On the contrary, combination of HisB26 with methylation in the B25 – B26 position leads to a “super active“ analogue [NMeHisB26]-des-tetrapeptide (B27-B30) insulin. A further similar analogue [NMeAlaB26]-des-tetrapeptide (B27-B30) has also a high biological activity. Currently are both active analogues being tested in two top laboratories in the US and in Denmark (Š. Zórad).

- The MicroPET equipment enables to study distribution and effects of drugs, tumor development as well as the effect of treatment in living small laboratory animals. It is also a valuable tool especially for testing the effects and distribution of newly developed drugs (V. Štrbák)

C. THE RESEARCH STRATEGY AND FOCUSING OF THE RESEARCH ACTIVITIES OF THE INSTITUTE OVER THE NEXT 4 YEARS

C.3.i Present state of knowledge and status of ongoing research related to subject of the Concept, from both international and national perspective

The global trends in experimental and clinical endocrinology are concentrating at elucidation of the neuroendocrine regulatory processes with special emphasis on assessments of their significance for impairments of pathogenesis of important non-infectious diseases, on understanding of mutual relations of the neural, endocrine and immune systems.

In the field of neuroendocrinology, increasing evidence has accumulated supporting the fact that neuroendocrine factors are involved in the pathogenesis and course of several mental disorders. In particular, exposure to intensive or chronic stress stimuli and dysregulation of stress hormone release play an important role in currently highly prevalent depressive disorders. The main research focus turned from classical monoaminergic neurotransmitters to the factors participating in neural plasticity and neurodegeneration. The influence of stress exposure on the susceptibility to the development of depression is thought to be based on both genetic and environmental factors. The environmental factors include prenatal and perinatal exposure to demanding events and the present knowledge allows to suggest an important role of neuroendocrine alterations in long-term consequences. Measurements and correlations of genetic variations, neuroendocrine changes and psychological characteristic are likely to reveal new aspects for the treatment and prevention of mental disorders.

Intensive attention is being paid to investigations of the endocrine functions of the various adipose tissue depots, to the role of the many molecules being either produced inside (e.g. adipokines) or being brought into the adipose tissue via blood stream (e.g. cytokines, circulating blood elements) for the origin and progression of the low-grade systemic inflammation and related disease processes. The research further focuses at deeper elucidation of the mechanism of hormone action with a special accent on regulation of gene expression for enzymes, receptors, transcription factors which could be of great importance for development of socially important diseases like obesity, type 2 diabetes, atherosclerosis, cardiovascular disease, hypertension etc.

More recently several gene defects have been identified which modulate the hormone receptor cell signaling pathways causing obesity, insulin resistance and atherosclerosis. Analysis of gene polymorphism or mutation in human subjects is used for detection of risk factors for development of obesity, the metabolic syndrome, monogenic forms of diabetes, type 2 diabetes and cardiovascular diseases. Pharmacogenomics data (e.g. in diabetes, lipids, cardiovascular medicine, in psychiatry) are also emerging indicating to new possibilities for personalization of the diagnostics and treatment to the individual patient.

The hormone and cytokine receptor transgenic and specific gene knockout animals are used in studies aimed at identification of the ethiopathogenesis of diseases states like the metabolic syndrome, diabetes and its complications or psychiatric disorders. The cell membrane initiated action of hormone ligand for nuclear receptors (e.g. steroid or thyroid hormones) and their effects on transcription processes are studied. The idea of a synergistic coupling between membrane initiated and genomic action of hormone revises fundamentally the cell signaling pathways in endocrinology. Alternative pathways for regulation of biosynthesis and secretion of hormones and other active molecules are being intensively sought as new drug targets.

Due to a striking methodological progress over the last decades in all areas of medicine and molecular biology, there are much greater possibilities and much less ethical concerns than in the past to use for research purposes samples of human origin. The high throughput techniques at the DNA, RNA and/or protein level allow running of hundreds of parameters in very small amounts of human material, which is certainly more informative for the scientific progress, more ethical to the patients and/or volunteers. Beside these analyses, further continues the use of selected animal models with various genetic modifications, tissue cultures of selected cell lines of both human and animal origin for solution of mechanistic questions arising from studies of the endocrine system-related human diseases.

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In harmony with the aforementioned, all around Europe large genotype and phenotype repositories are being established on the general population and/or selected diseases states. They allow rapid responses of the research community to newly emerging challenges in their area of interest, by simply employing the research tools of molecular biology and genetics on the samples readily available due to the existing PC supported databases.

3.ii. Organisation´s role of significance in overall research effort within the field of the Concept on both national and international scales

The Institute is the only scientific research place in the Slovak republic which deals with the basic explorations in the area of endocrinology combined with research outputs specifically aimed for the use in clinical practice. The Institute is an internationally accepted and renowned research institution, which has been over several decades engaged into research of the function and regulation of the thyroid gland in various disease states. Furthermore, the Institute has won an outstanding position in the research of neuroendocrine response to stress situations; in particular in the area of function of the sympathoadrenal system after application of various stress stimuli including the space flight of both, the rats and the astronauts. International recognition has been also received with respect to new insights into the role of neuroendocrine factors in depression and anxiety. Studies on the role of cell volume changes for regulation of peptide hormone secretion have also a pioneering character.

A very intensive attention has been paid at the Institute in the last couple of years to identification of various disorders of lipid metabolism, and production of various adipokines and cytokines in adipose tissue in relation to the low grade systematic inflammation and origin of the metabolic syndrome. The Institute has become also the leading center in the screening and DNA diagnostics of the various forms of monogenic diabetes in Slovakia and has established the first DNA repository in diabetology in this country. Of utmost importance for the Slovak endocrinology has been also the publication of the postgraduate textbook on basic and clinical endocrinology which is being used as the main textbook for taking the specialization boards in clinical endocrinology in this country. Two leading researchers – employees of this Institute served as editors. Moreover, researchers from this Institute contributed in total to completion of 20 chapters of this book. The textbook received the Award of the Slovak Literature Foundation for the Best Book in section Medicine and Molecular Biology as published in 2004.

A national reward of the current achievements of the Institute has been also the awarding of our Institute by the status of an Centre of Excellence presented to us by the Slovak Academy of Sciences SAV based upon the project entitled “Center of Excellence for research of neuroendocrine mechanisms in the pathogenesis of weighty diseases /acronym CENDO/”. The project anticipates an active collaboration with the Slovak Health University, with the faculty of Natural Sciences as well as continuation of collaboration with other research and health care organizations.

An important international recognition of the Institute’s research has been the awarding of our Institute with the statute of a Centre of Excellence by the European Commisssion in Brussels, Belgium. This was received after a successful evaluation of our project entitled „Reduction of negative impact of environmental factors on human health“. With participation of important foreign researchers several research projects were carried out, e.g. in the area of regulation of vasoactive hormone secretion in stress (H. Hinghofer-Szalkay), investigations of neuroendocrine regulations of behaviour and brain plasticity (B. Johansson), hormone secretion in relation to mental stress (I. Loder), or mechanisms of insulin secretion regulation in relation to changes of cell volume (M. Ritter). Within the CE project, several long-term study stays of Post-Docs from abroad took place, who worked on, e.g. regulation of fatty acid oxidation in liver and skeletal muscle by leptin in relation to insulin resistance development (S.Wein, FRG), on elucidation of central regulatory mechanisms of stress-induced prolactin secretion (I. Bodnár, Hungary). Moreover, two Post-Docs (L. Rondahl, Sweden and S. Mostböck, Austria) studied the effect of heavy metals appearing in pollutants on nuclear receptor pathway. A PhD student from Greece (A. Makatsori) had studied pharmacological possibilities for alteration of stress in man and animals. The important international position of our Institute is underlined by the participation of our research teams in 6 international projects within the EU Framework Programs. The aforementioned encompasses within the 5 th FP the following projects, i.e. the PCBRISK (Evaluating human health risk from low-dose and long-term PCB exposure), VITAGE (Vitamin A, vitamin E and carotenoid status and metabolism during ageing: Functional and nutritional consequences), ENDOMET (Dysregulation of endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticisers) and the DROSDEL (Construction of a new Drosophila duplication collection).

Within the 6th FP, the research teams of this Institute participate in the following projects: CASCADE (Chemical contaminants in the food chain) and in the DANUBIOBANK (The Danubian Biobank Initiative: Towards Information-Based Medicine).

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Several research groups of our Institute had been active in research projects supported by the biomedical programs of the EC like the COST B17 (Insulin resistance, obesity and diabetes mellitus in the elderly: Fatty acid oxidation and insulin resistance) or other international organizations, e.g. NATO (Genes in Control of Apoptosis during Drosophila metamorphosis).

Three research projects have been supported within the scheme of the Slovak-American scientific and technical collaboration scheme, e.g. the project on „Ethanol and cell swelling induced peptide secretion: intracellular signalling and regulation“; „Function and molecular interactions of the LAMMER kinase“ and the „Stressor-specific regulation of catecholamine biosynthetic enzyme gene expression“.

Successful scientific collaboration has been pursued also at further important international projects, i.e. on „Environmental influences on hormone release during stress in humans: continuation of previous common studies“, which has been executed within an Austrian-Slovak collaboration, and a project with a  Greek partner dealt with „Environmental stimuli and neuronal plasticity“. Within a bilateral collaboration with a US partner successfully continued the work at the project „Slovakia PCB Exposures and Early Childhood Development“. The very important and highly innovative results on „Pharmacogenomics of Permanent Neonatal Diabetes“ have been achieved within a long-term bilateral collaboration with the Biomedical Research Institute of the Exeter University in the UK.

Several leading scientists of the Institute have been members of the editorial/international boards of various international professional journals what resembles their high professional credit in their professional community abroad. Out of the 9 colleagues who are active in the editorial boards, we like to underline particularly the positions of the Executive Editor for Europe in the journal Cellular and Molecular Neurobiology (USA), the Associate Editor in the official journal of the European Association for the Study of Diabetes, i.e. Diabetologia, members on boards of Stress (USA), Neuroendocrinology (USA), Neuroscience News (USA), and Archives Physiol. Biochemistry (Netherlands).

3.iii. Objectives of the ConceptThe main lines of the thematic orientation for scientific research activities of the Institute for the next 4

years shall involve:

A/ research of mechanisms of the neuroendocrine regulation of body functions with special emphasis upon identification of the effects of genetic background, gender, physiological, pharmacological or environmental factors or interventions on the responses to various stress situations, and elucidation of their changes in pathogenesis of various diseases, including those of the cardiovascular and immune system, rheumatic disorders, and the physiology and pathology of behaviour.

B/ investigations on the action of hormones, cytokines and other biologically active molecules of endogenous and/or exogenous origin influencing metabolic processes both in cells /in vitro/ conditions and in integrated organism /in vivo/. Furthermore, molecular biology tools will be employed to disclose the role of gene polymorphisms and mutations for regulation of metabolic pathways in health and disease at the DNA, RNA and protein level. The aforementioned shall be carried out with the aim to unmask the presence of disease risk factors, to elucidate detail mechanisms of disease origin and development, and to innovate diagnostics and treatment of selected diseases /e.g. obesity, diabetes, specific oncology diseases etc.).

In the area of neuroendocrine regulations, the research shall focus at:1. physiology and pharmacology of the catecholaminergic system in response to stress, in particular ata) elucidation of the genetic nature of the adaptive and maladaptive processes during adaptation to a long-term

acting of psychological or physical stress stimulib) evaluations of the molecular genetic nature of the hyper-reactivity of organism adapted to one type of stress stimulus after their exposure to a different stressor

c) studies of the adaptation processes to repeated exposure to different stressors in a new line of genetically modified animals lacking the key enzyme of catecholamine synthesis, i.e. the PNMT

d) broadening of knowledge on the genetic apparatus of catecholamine biosynthesis in the adipose tissue which may be critically involved into the stress response and into deterioration of the insulin action as well

e) mapping of changes of the sympatho-adrenal and hypothalamic-hypophyseal-adrenocortical system in a rat model of the Alzheimer disease

2. mental disorders, in particular at a) investigations of principles of the neuroendocrine regulation of the organism in conditions of stress and their

relation to the induction and development of mental impairment. Attention will be also given to identification of gender differences in the regulatory processes of the body as the appearance of individual mood disorders seems to be deeply sex dependent,

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b) elucidation of the degree to which the neuroendocrine changes in stress can be determined by the individual psychologic and behavioural characteristics with special emphasis on anxiosity and depressive situations and

c) studies of prenatal stress effects with the aim to test possible long-term consequences for coping with stress depending on the genetic background and epigenetics

The aforementioned goals shall be executed in both, the animal and human models, as well as in specific patients selected in collaboration with the clinical psychiatry department in Bratislava

3. rheumatic diseases, in particular at a) elucidation of the mechanism for the reduced adrenocortical and adrenomedullary function in rheumatic

patientsb) following up the consequences of the above endocrine changes on the regulation of immune functions

looking at the effect of cortisol, dehydroepiandrosterone and catecholamines on cytokine production, expression of receptors mediating the antigen presentation, apoptosis and other functions

c) contribution of the genetic predisposition to these endocrine changes in the first degree relativesd) studying the role of the chronic inflammation on lipid and carbohydrate metabolism with parallel

measurements of production of proinflammatory cytokines in subcutaneous adipose tissuee) investigations of the subsystems of the autonomic nervous system in rheumatic patientsThe goals of this project shall be achieved in the ongoing long-lasting collaboration with the Institute of Rheumatic Diseases in the town Piestany

4. hypertension and diabetes, in particular ata) investigations of the subsystems of the autonomic nervous system in diabetic patientsb) elucidation of mechanisms of insulin resistance and insulin hypersecretion in subjects with juvenile

hypertension at the level of tissuesThe goals of this project shall be achieved in the ongoing long-lasting collaboration with the Institute of Rheumatic Diseases in the town Piestany.

5. tumorigenesis, in particular ata) studies aimed at ascertaining of the n. vagus participation in monitoring and modulation of function of the

immune system components with a special emphasis on the role of n. vagus in tumorigenesisb) definition of humoral and neural pathways participating in transmission of information about tumorigenesis

to the central nervous system andc) identification of those brain areas which are receiving the above information, digest them and reciprocally

intervene with the tumorigenesis processes d) describing the role of the vagus nerve in regulation of inflammatory processes with emphasis on the role of vagus

stimulation for induction of the ischemia-reperfusion liver damage and the role of spleen in these processes. The goals of this project shall be achieved in close cooperation with the Institute of Pathophysiology of the Comenius University School of Medicine in Bratislava.

In the area of hormone secretion and action and their role in pathogenesis of diseases, the research shall focus at the:

6. role of adipose tissue and low-grade systemic inflammation for the metabolic syndrome in man , in particular at a) analyses of the gene expression for transcription factors involved in the origin and maintenance of the

inflammatory processes in simple obesity, glucose intolerance and growth hormone deficiencyb) measurements of the oxidative capacity of the mitochondria and their gene expression for relevant enzymes

in the above situationsc) pathogenesis of the subclinical inflammation processes in circulation, adipose and muscle tissue in patients

with morbid obesity before and after surgical intervention /gastric banding/d) testing the hypothesis that the decreased amount of adipose tissue in patients with the chronic obstructive

disease of the lung produces higher amounts of adipokines and leads thus to metabolic abnormalities typical for low-grade systemic inflammation

7. role of the renin-angiotensin system in the adipose tissue of rats, in particular ata) measurements of the components of the renin-angiotensin system in the adipose tissue in response to high

fat feedingb) up-regulation of the angiotensin AT1 receptors in the fat tissue during diet- or genetically-induced obesity of ratsc) investigation of changes in the cellular organization of the adipose tissue and in the adipokine production

after blockade of the AT1 receptorsd) comparison of the action of the ACE inhibitors and blockers of AT1 receptors on the cellularity of the

adipose tissue and adipokine production

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8. DNA diagnostics and screening of monogenic forms of diabetes in Slovakia, in particular ata) continuation of the ongoing activities in DNA diagnostics of monogenic diabetes across the whole countryb) active screening for mutation carriers yet without the manifest disease in all blood relatives of the positive

probands having clinically manifested diabetesc) active counselling on the DNA based recommendations for change of treatment /insulin vs. sulphonylurea or

diet/ and long-term clinical physiology monitoring of those patientsd) identification of new mutations and collection of extensive phenotypes in order to enable proper structure-

function studiese) setting-up the high throughput analytical performance profile /i.e. dHPLC mutation pre-screening plus

mutation identification via ABI direct sequencing/ for all types of monogenic diabetes /currently about 15 diagnoses/

f) maintenance of the DNA repository, opening of a sub-registry on monogenic diabetes within the National Children Diabetes Registry and loading it up with the gene- and phenotypic data obtained

9. alternative mechanisms of hormone secretion and action, in particular ata) identification of a novel mechanism of secretion and exocytosis of peptide hormones with accent at

possibilities to influence the insulin secretionb) characterization of the signaling pathway leading from cell swelling to exocytosis of insulin and its

comparison with the glucose-induced insulin secretion pathwayc) classification of the function and regulation of peptides in heart with emphasis on the appearance of TRH in

the heart, including its regulation and interaction with the renin-angiotensin system

10.insulin analogues and their mechanisms of action, in particular at a) identification of the effects of the super potent insulin analogues on insulin aggregation andb) the interaction of insulin with specific receptors

11. the retinoids and rexinoids, in particular ata) elucidation of the mechanism of action of both, the retinoids and rexinoids as well as of their structural

derivatives b) investigation of mechanism of action of the steroid hormone dihydroxyvitamine D3 and its structural derivatives with their potentially anti-cancer effects

c) the use of the relevant analytical methodology in human endocrinology, especially for measurements of expression of subtypes of the nuclear receptors of the all-trans retinoic and 9-cis retinoic acids in the tumor tissue of the thyroid gland, mammary gland and in the prostate with the possibility to use retinoic acid and its derivatives in treatment of oncological diseases

d) studies on the negative effects of chemical compounds on the regulatory mechanisms mediated via the nuclear receptors of retinoic acids, or hormones of the thyroid gland and estrogens

12.on further explorations of endocrine disruptors, in particular ata) studies on the mechanisms of action of the individual phthalate/phenols derivatives and their combinations

on the cell growth via elucidation of the intracellular and nuclear mechanisms of action of the estrogen receptor-α

b) identification of the relation between the length of exposition and dosage of the individual compounds and their mixtures tested in relation to cell proliferation with the aim to define safe exposition dosages, which do not induce cell proliferation

13.characterisation of molecular and cellular mechanisms of action of the Juvenile hormone /JH/ elucidation of the programmed cell death, in particular at

a) learning the properties of a so far not known JH receptorb) deepening of knowledge of its signaling pathway used for its effect on morphogenesisc) explaining the evolutionary consequences of this developmentd) investigations of the hormone-induced apoptosis of the Drosophila salivary glande) learning the molecular and genetic interactions between the individual components of this signaling pathway

in order to understand the origin of the Parkinson, Huntington, Alzheimer or Lou-Gehrig diseases

3.iv. Proposed strategies and methods to be applied, and time schedule

The research strategy as outlined above can be pursued proposed that the financial requirements of the individual projects shall be met in full over the years to come. The current situation with an overview of the type and duration of the research grant support is displayed in the table below:

Objective number

Types of Research Grants*

Number of projects in each category

Time schedule

VEGA APVV EC ESF NATO COST Other From-To

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1 X X 2007-09 2 X X X X 2007-09 3 X 2007-08 4 X X X 2007-09 5 X, X X X 2007-09 6 X, X X X 2007-09 7 X 2007 8 X X X X 2007-09 9 X X X X 2007-0910 X 200711 X X X 2007-0912 X, X X 2007-0913 X X 2007-09

* Types of Research Grants: VEGA = Scientific Grant Agency /small grants/, APVV = Agency for Support of Science and Development /the major research grant agency in Slovakia/, EC = European Commission /6th and 7th FP/, ESF = European Social Fund, COST = Cooperation in Science and Technology

Beside external fund raising, which is essential for successful accomplishment of any research project per se, it will be necessary to continue in the broad international collaboration /for more details see Appendix No. 1/. In this respect, our Institute has a long and proven track which is resembled at best in the Institute’s List of Publications and their citations, majority of which comes from impacted foreign journals.

The scientific goals of the Institute as outlined for the four years to come, shall require a significant move forward in the overall methodological development. The research strategy shall require beside a series of currently used methods of molecular biology, genetics, biochemistry, histochemistry and clinical physiology development of a series of other techniques, in particular

/hardware already available/:- dHPLC pre-screening and identification of new mutations by direct sequencing for all types of

monogenic diabetes /all hardware already available and working/- Real time PCR assays of nuclear receptors and reversed transcription of them- Electrophoretic mobility shift assay

/hardware to be obtained or to be used at collaborating centers/:- DNA and protein arrays- Fluorescence and laser confocal microscopy- Transmission microscopy and reverse electron microscopy- In situ hybridization with non-radioactive markers- Laser micro dissection of specific areas in the brain- Gene transfection and gene silencing

Potential risks for fulfillment of the Concept encompass mainly low institutional financing from the Academy resources coming in from the state budget, constant increase in the energy prices, persisting administrative and financial obstacles for joining and utilization of the EU structural funds, very low increase of wages and insufficient inflow of new permanent positions for middle-age investigators. In fact, currently at the Institute we experience a large gap between the researchers in their fifties and the new generation in late thirties, of whom we have currently employed just three investigators, out of them two are working abroad for more than three years so far and their return chances are rather low. Lastly, additional finances shall be needed to keep up with the proposed methodological advancement of the Institute, in particular for purchase of larger pieces of hardware, requiring capital outlays.

III. Partial indicators of the main activities:

1. Research output

i. List of the selected publications documenting the most important results of

basic research. Total number of publications in the whole assessed period

should not exceed the average number of the research employees

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2003 (IF 2002)1. KLIMES I, WESTON K, KOVACS P, GASPERIKOVA D, JEZOVA D, KVETNANSKY R,

THOMPSON JR, SEBOKOVA E, SAMANI NJ: Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome. Diabetologia, 46: 352-358, 2003. IF= 5,136

2. BRTKO J, THALHAMER J: Renaissance of the biologically active vitamin A derivatives: Established and novel directed therapies for cancer and chemoprevention. Current Pharmaceutical Design, 9: 2067-2077, 2003. IF= 4,692

3. ROVENSKY J, IMRICH R, KOSKA J, KOVALANCIK M, KILLINGER Z, PAYER J, VIGAS M, JEZOVA D: Cortisol elimination from plasma in premenopausal women with rheumatoid arthritis. Ann Rheum Dis, 62: 674-6, 2003. IF=3,593

4. MONCEK F, AGUILERA G, JEZOVA D: Insufficient activation of adrenocortical but not adrenomedullary hormones during stress in rats subjected to repeated immune challenge. J Neuroimmunol, 142: 86-92, 2003. IF= 3,577

5. NAJVIRTOVA M, GREER SE, GREER MA, BAQI L, BENICKY J, STRBAK V: Cell volume induced hormone secretion: Studies on signal transduction and specificity. Cell Physiol Biochem, 13: 113-122, 2003. IF= 3,059

6. MICUTKOVA L, KVETNANSKY R, KRIZANOVA O: Repeated immobilization stress reduces the gene expression of type 1 and 2 IP3 receptors in stellate ganglia. Neurochem Int, 43(6): 557-561, 2003. IF= 3,040

7. MICUTKOVA L, RYCHKOVA N, SABBAN EL, KRIZANOVA O, KVETNANSKY R: Quantitation of changes in gene expression of norepinephrine biosynthetic enzymes in rat stellate ganglia induced by stress. Neurochem Int, 43(3): 235-242, 2003. IF= 3,040

8. MAKATSORI A, DUNCKO R, SCHWENDT M, MONCEK F, JOHANSSON BB, JEZOVA D: Voluntary wheel running modulates glutamate receptor subunit gene expression and stress hormone release in Lewis rats. Psychoneuroendocrinol, 28: 702–714, 2003. IF= 2,982

9. PIRNIK Z, MIKKELSEN JD, KISS A : C-Fos induction in the rat deep cerebellar and vestibular nuclei after central administration of colchicine: a qualitative and quantitative time-course study. Brain Res Bull, 61(1): 63-72, 2003. IF= 2,283

10. UKROPEC J, RESELAND JE, GASPERIKOVA D, DEMCAKOVA E, MADSENL, BERGE RK, RUSTAN AC, KLIMES I, DREVON CA, SEBOKOVA E: The hypertriglyceridemic effect of dietary n-3 fatty acids is associated with increased β-oxidation and reduced leptin expression. Lipids, 38 (10): 1-7, 2003. IF= 2,044

2004 (IF 2003)1. BENNASROUNE A, FICKOVA M, GARDIN A, DIRRIG-GROSCH S, AUNIS D, CREMEL G,

HUBERT P: Transmembrane peptides as inhibitors of ErbB receptor signaling. MOL BIOL CELL 15(7):3464-74, 2004. IF = 7.454

2. ZAKOVA L, BARTH T, JIRACEK J, BARTHOVA J, ZORAD S: Shortened insulin analogues: marked changes in biological activity resulting from replacement of TyrB26 and N-methylation of peptide bonds in the C-terminus of the B-chain. BIOCHEM 43 :2323-2331, 2004. IF = 3.922

3. IMRICH R , ROVENSKY J, ZLNAY M, RADIKOVA Z, MACHO L, VIGAS M, KOSKA J: Hypothalamic-pituitary-adrenal axis function in ankylosing spondylitis. ANN RHEUM DIS 63: 671-674, 2004. IF = 3,827

4. KUBOVCAKOVA L, KRIZANOVA O, KVETNANSKY R : Identification of the aromatic L-amino acid decarboxylase gene expression in various mice tissues and its modulation by immobilization stress in stellate ganglia. NEUROSCIENCE 126: 375-380, 2004. IF = 3,601

5. MONCEK F, DUNCKO R, JOHANSSON BB, JEZOVA D: Effect of environmental enrichment on stress related systems in rats. J NEUROENDOCRINOL 16: 423-431, 2004. IF = 3,418

6. BODNAR I, MRAVEC B, KUBOVCAKOVA L, TOTH EB, FULOP F, FEKETE MIK, KVETNANSKY R, NAGY GM: Stress- as well as suckling-induced prolactin release is blocked by a structural analogue of the putative hypophysiotrophic prolactin-releasing factor, salsolinol. J NEUROENDOCRINOL 16: 208-213, 2004. IF =3,418

7. PIRNIK Z, MRAVEC B, KISS A : Fos protein expression in mouse hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei upon osmotic stimulus: colocalization with vasopressin, oxytocin, and tyrosine hydroxylase. NEUROCHEM INT 45(5): 597-607, 2004. IF = 3,261

8. MAKATSORI A, DUNCKO R, MONCEK F, LODER I, KATINA S, JEZOVA D: Modulation of neuroendocrine response and non-verbal behavior during psychosocial stress in healthy volunteers by

17

the glutamate release inhibiting drug lamotrigine. NEUROENDOCRINOL 79:34-42, 2004. IF= 2,8449. POHORECKY LA, BLAKLEY GG, KUBOVCAKOVA L, KRIZANOVA O, PATTERSON-

BUCKENDAHL P, KVETNANSKY R: Social hierarchy affects gene expression for catecholamine biosynthetic enzymes in rat adrenal glands. NEUROENDOCRINOLOGY 80: 42-51, 2004. IF =2,844

10. JEZOVA D, MLYNARIK M , ZELENA D, MAKARA GB: Behavioral sensitization to intermittent morphine in mice is accompanied by reduced adrenocorticotropine but not corticosterone responses. BRAIN RES 1021(1):63-8, 2004. IF = 2,474

2005 (IF 2004)1. BROUWERS FM, PETRICOIN EF, KSINANTOVA L, BREZA J, RAJAPAKSE V, ROSS S,

JOHANN D, MANNELLI M, SHULKIN BL, KVETNANSKY R, EISENHOFER G, WALTHER MM, HITT BA, CONRADS TP, VEENSTRA D, MANNION DP, WALL MR, WOLFE GM, FUSARO VA, LIOTTA LA, PACAK K: Low molecular weight proteomic

2. information distinguishes metastatic from benign pheochromocytoma. ENDOCR RELAT CANCER 12 (2): 263-272, 2005. IF =4,597

3. IMRICH R , ROVENSKY J, MALIS F, ZLNAY D, KILLINGER Z, KVETNANSKY R, HUCKOVA M, VIGAS M, MACHO L, KOSKA J: Low levels of dehydroepiandrosterone sulphate in plasma, and reduced symphatoadrenal response to hypoglycaemia in premenopausal women with rheumatoid arthritis. ANN RHEUM DIS 64 (2): 202-206, 2005. IF = 3,916

4. IMRICH R , ROVENSKY J, VIGAS M: Different threshold for prolactin response to hypoglycaemia in patients with rheumatoid arthritis? ANN RHEUM DIS 64 (2): 515-516, 2005. IF = 3,916

5. KLIMES I , WESTON K, GASPERIKOVA D, KOVACS P, KVETNANSKY R, JEZOVA D, DIXON R, THOMPSON JR, SEBOKOVA E, SAMANI J: Mapping of genetic determinants of the sympathoneural response to stress. PHYSIOL GENOM 20: 183-187, 2005. IF = 3,855

6. PISTOVCAKOVA J, MAKATSORI A, SULCOVA A, JEZOVA D : Felbamate reduces hormone release and locomotor hypoactivity induced by repeated stress of social defeat in mice. EUR NEUROPSYCHOPHARMACOL 15: 153-158, 2005 IF = 3,545

7. STEFANIK P, MACEJOVA D, MRAVEC B, BRTKO J, KRIZANOVA O: Distinct modulation of a gene expression of the type 1 and 2 IP3 receptors by retinoic acid in brain areas. NEUROCHEM INT 46 (7): 559-564, 2005. IF = 3,211

8. PIRNIK Z , JEZOVA D, MIKKELSEN JD, KISS A : Xylazine activates oxytocinergic but not vasopressinergic hypothalamic neurons under normal and hyperosmotic conditions in rats. NEUROCHEM INT 47(7): 458-465, 2005. IF = 3,211

9. BACOVA Z , BENICKY J, LUKYANETZ EE, LUKYANETS IA, STRBAK V: Different Signaling Pathways Involved in Glucose and Cell Swelling-Induced Insulin Secretion by Rat Pancreatic Islets in Vitro. CELL PHYSIOL BIOCHEM 16: 59-68, 2005. IF = 3,093

10. MRAVEC B, BODNAR I, UHERECZKY G, NAGY GM, KVETNANSKY R, PALKOVITS M: Formalin attenuates the stress-induced increase in plasma epinephrine levels. J NEUROENDOCRINOL 17 (11): 727-732, 2005. IF = 2,920

2006 (IF 2005)1. PEARSON ER, FLECHTNER I, NJOLSTAD PR, MALECKI MT, FLANAGAN SE, LARKIN

B, ASHCROFT FM, KLIMES I, CODNER E, IOTOVA V, SLIGERLAND AS, SHIELD J, ROBERT JJ, HOLST JJ, CLARK PM, ELLARD S, SOVIK O, POLAK M, HATTERSLEY AT: for the Neonatal Diabetes International Collaborative Group (including GASPERIKOVA D, STANIK J): Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N ENGL J MED 355 (5): 467-77, 2006. (IF=44,016)

2. KUBOVČÁKOVÁ L, MIČUTKOVÁ L, BARTOŠOVÁ Z, SABBAN EL, KRIŽANOVÁ O, KVETŇANSKÝ R: Identification of phenylethanolamine N-methyltransferase gene expression in stellate ganglia and its modulation by stress. J NEUROCHEM 97:1419-30, 2006. (IF=4.604)

3. IMRICH R , LUKAC J, ROVENSKY J, RADIKOVA Z, PENESOVA A, KVETNANSKY R, HUCKOVA M, VIGAS M, MACHO L, KOSKA J: Lower adrenocortical and adrenomedullary responses to hypoglycemia in premenopausal women with systemic sclerosis. J RHEUMATOL 33(11): 2235-2241, 2006 (IF=3,010)

18

4. TILLINGER A, NOVAKOVA M, PAVLOVICOVA M, LACINOVA L, ZATOVICOVA M, PASTOREKOVA S, KRIZANOVA O, KVETNANSKY R: Modulation of gene expression of the PNMT in the heart during immobilization stress by 6–hydroxydopamine. STRESS 9: 207–213, 2006 (IF=2.967)

5. BAČOVÁ Z , BAQI L, BEŇAČKA O, PAYER J, KRIŽANOVÁ 0, ZEMAN M, SMREKOVÁ L, ZORAD Š, ŠTRBÁK V: Thyrotropin-releasing hormone in rat heart: effect of swelling, angiotensin II and renin gene. ACTA PHYSIOLOGICA 187:313-319, 2006 (IF=2,865)

6. DUNCKO R, MAKATSORI A, FICKOVA E, SELKO D, JEZOVA D: Altered coordination of the neuroendocrine response during psychosocial stress in subjects with

high trait anxiety. PROG. NEUROPSYCHOPHARMACOL. BIOL PSYCHIATRY 30: 1058-1066, 2006 (IF=2,769)

7. WILSON TG, WANG S, BEŇO M, FARKAŠ R: Wide mutational spectrum of a gene involved inhormone action and insecticide resistance in Drosophila melanogaster. MOL GENET GENOMICS 276 (3): 294-303, 2006 (IF=2,632)

8. KISS A , SØDERMANA, BUNDZIKOVA J, PIRNIK Z, MIKKELSEN JD: Zolpidem, a selective GABAA receptor α1 subunit agonist, induces Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat. BRAIN RES BULL 71(1-3), 200-207, 2006. (IF=2.481)

9. ZORAD S , DOU J, BENICKY J, HUTANU D, TYBITANCLOVA K, ZHOU J, SAAVEDRA J.M.: Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy and increases markers of insulin sensitivity adiponectin and PPARγ. EUR J PHARMACOL 552: 112 = 122, 2006 (IF=2,477)

10. RADIKOVA Z, PENESOVA A , CIZMAROVA E, HUCKOVA M, KVETNANSKY R, VIGAS M, KOSKA J: Decreased pituitary response to insulin induced hypoglycemia in young lean male patients with essential hypertension. J HUM HYPERTENS 20(7): 510-516, 2006 (IF=2,405)

ii. List of monographs/books published abroad

PACAK K, AGUILERA G, SABBAN EL, KVETNANSKY R (Eds.): Stress – Current

Neuroendocrine and Genetic Approaches. NY Acad Sci, New York, p. 1-590, 2004

List of chapters published in monographs abroad

1. STRBAK V, BENICKY J , GREER SE, BACOVA Z, NAJVIRTOVA M, GREER MA: Cell swelling-induced peptide hormone secretion. In: Lauf PK, Adragna NC (eds.) Cell Volume and Signaling, Advances in Experimental Medicine and Biology, New York, Springer Science and Business Media, vol 559, 2004, p.325-330.

2. BAČOVÁ Z, BENICKÝ J, GREER MA, RITTAR M, GREER SE, ŠTRBÁK V: Cell volume induced hormone secretion: studies on signal transduction and specificity. In: Receptors Channels Messengers, Platon Kostyuk, Elena Lukyanetz (eds), DUS, Kiev 2005, p. 212-219.

3. BENICKÝ J, KRIŽANOVÁ O, ŠTRBÁK V : Effect of thyrotropin releasing hormone (TRH) on insulin secretion. In: P. Joseph-Bravo(ed) Molecular Endocrinology, Research Signpost, Trivandrum, Kerala, 2006, pp 109-125.

4. JEZOVA D , SCHWENDT M: Adrenal glutamate receptors: a role in stress and drug addiction? In: Glutamate Receptors in Peripheral Tissue: Excitatory Transmission Outside the CNS. Gill, S. and Pulido O. (eds.). Kluwer Academic/Plenum Publishers: New York, 2005, pp. 169-178.

5. ŠTRBÁK V : Cell Volume and Peptide Hormone Secretion. In: Lang F. (ed): Mechanisms and Significance of Cell Volume Regulation. Contrib. Nephrol. Basel, Karger, 2006, vol. 152, pp. 210-220.

19

iii. List of monographs/books published in Slovakia

1. Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), AEP, Bratislava, 2004, 910 pages.

iv. List of other scientific outputs specifically important for the Organisation

1. Všeobecná a klinická endokrinológia (Basic and clinical endocrinology).(A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), AEP, Bratislava, 2004, pp. 1-910.

List of chapters published in monographs in Slovakia

1. JEŽOVÁ D, KRISTOVÁ V, KÁKOŠOVÁ V. Interakcie hormonálnychliečiv. (Interactions of hormonal medicaments) In: Interakcie liečiv v klinickej praxi, L. Magulová, L. Božeková, M. Kriška (eds.), Slovak Academic Press, Bratislava, 135-148, 2003.

2. Langer, P.: Ciele a spôsoby vedeckého bádania (Aims and methods of scientific research). In: Hulín, I.: Úvod do vedeckého bádania I., Bratislava, Slovak Academic Press, s. 151-172, ISBN80-89104-29-0, 2003.

3. HUDÁK J, VLČEK D, FARKAŠ R a kol.: Encyklopédia biológie, zv. 1, Genetika, molekulárna biológia a evolúcia. (Encyclopedy of biology, Vol. 1, Genetics, molecular biology and evolution). Slovenské pedagogické nakladateľstvo, Bratislava, 2005.

4. BRTKO J : Hormone action mediated via nuclear receptors /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 23-29, AEP, Bratislava, 2004.

5. BRTKO J , THALHAMER J: Gene expression as a response to the hormone action /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 101-106, AEP, Bratislava, 2004.

6. GASPERIKOVA D , SEBOKOVA E, KLIMES I: Mitochondrial DNA and diabetes /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 620-623, AEP, Bratislava 2004.

7. HUCKOVA M : Laboratory methods for hormone analyses /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 62-70, AEP, Bratislava 2004.

8. JEZOVA D : Suprahypothalamic regulation of endocrine functions /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 107-116, AEP, Bratislava, 2004.

9. JEZOVA D: Pathophysiology of the sympatho-adrenal-medullary system /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 403-411, AEP, Bratislava, 2004.

10. KLIMES I , SEBOKOVA E, TKAC I: Metabolic syndrome /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 610-613, AEP, Bratislava 2004.

11. LANGER P : Endocrine disruptors /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 51-58, AEP, Bratislava 2004.

20

12. LANGER P : Pathophysiology of the thyroid gland /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 189-201, AEP, Bratislava 2004.

13. LANGER P : General ethiology and pathogenesis of thyreopathies /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 202-211, AEP, Bratislava 2004.

14. LANGER P : Laboratory diagnostics of the thyroid gland diseases /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 212-218, AEP, Bratislava 2004.

15. NEMEC J, ZAMRAZIL V, RACEK P, CHYTRY P, LANGER P: Tumors of the thyroid gland /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 275-281, AEP, Bratislava 2004.

16. MACHO L : Biosynthesis, secretion, transport and metabolism of hormones /in Slovak/. In.: Všeobecná a klinická endokrinologia (A. Kreze, P. Langer, I. Klimeš, L. Starka, J. Payer, J. Michálek eds.), s. 7-15, AEP, Bratislava, 2004.

17. MACHO L, LANGER P, KREZE A, STARKA S: Pathophysiology of the adrenal cortex. In: Všeobecná a klinická endokrinológia, (A.Kreze, P.Langer, I. Klimeš, L. Starka, J. Payer, J. Michálek eds.), s. 351-359, AEP, Bratislava, 2004.

18. MACHO L: History of endocrinology. The Institute of Experimental Endocrinology /in Slovak/. In Všeobecná a klinická endokrinologia (A. Kreze, P. Langer, I. Klimeš, L. Starka, J. Payer, J. Michálek eds.), s. XVIII-XIX, AEP, Bratislava, 2004.

19. SEBOKOVA E , KLIMES I: Endocrinology of the adipose tissue /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 515-521, AEP, Bratislava 2004.

20. SEBOKOVA E , GASPERIKOVA D, KLIMES I: Membrane receptor-mediated hormone actions /in Slovak/. In: Všeobecná a klinická endokrinológia (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 16-22, AEP, Bratislava 2004.

21. VIGAS M : Endocrine system and stress. In: Všeobecná a klinická endokrinológia. (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 30-35, AEP, Bratislava, 2004.

22. VIGAS M, KOSKA J : Pathophysiology of the hypothalamus-hypophysis system /in Slovak/. In: Všeobecná a klinická endokrinológia. (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), s. 117-131, AEP, Bratislava, 2004.

1. Table of research outputs

Table Research outputs shows research outputs in number of specified entries; these

entries are then divided by FTE employees with a university degree (from Tab. Research

staff) for all Organisation at the respective year; finally these entries are divided by the

total salary budget (from Tab. Salary budget).

21

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

avera

ged

nu

mb

er

per

year

av. N

o. / F

TE

av. N

o. / sala

ry b

ud

get

chapters in monographs, books published abroad

0 0,00 0,00 1 0,03 0,07 2 0,05 0,14 2 0,05 0,13 5 1,3 0,03 0,09

chapters in monographs, books published in Slovakia

2 0,05 0,15 20 0,54 1,46 1 0,03 0,07 0 0,00 0,00 23 5,8 0,15 0,40

CC publications 37 1,01 2,77 46 1,23 3,35 37 0,98 2,52 39 1,06 2,48 159 39,8 1,07 2,76

scientific publications indexed by other databases

0 0,00 0,00 0,00 0,00 0,00 0,00 13 0,35 0,83 13 6,5 0,18 0,45

scientific publications in other journals

22 0,60 1,65 22 0,59 1,60 23 0,61 1,56 22 0,60 1,40 89 22,3 0,60 1,55

publications in proc. of international scientific

13 0,35 0,97 0,00 0,00 0,00 0,00 0,00 0,00 13 13,0 0,35 0,90

publications in proc. of nat. scientific conferences

0 0,00 0,00 0,00 0,00 0,00 0,00 0,00 0,00 0 0,0 0,00 0,00

active participations at international conferences

130 3,54 9,74 124 3,33 9,02 126 3,35 8,57 116 3,14 7,37 496 124,0 3,34 8,62

active participations at national conferences

30 0,82 2,25 17 0,46 1,24 8 0,21 0,54 12 0,33 0,76 67 16,8 0,45 1,16

total

Research outputs

2003 2004 2005 2006

2. Renormalized publications2

Renormalized publications = number of CC publications in the given year times

authorship’s portion of the Organisation times the journal impact factor in 2005 divided by

the median impact factor in the research field

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

Renormalized publications 25,1 0,68 1,88 86 2,30 6,26 35,2 0,94 2,39 35,7 0,97 2,27

2006

Renormalised publications

2003 2004 2005

2 This information is required only from the Organisations of the Section 2 of the Slovak Academy of Sciences.

22

3. Standard manuscript page count3

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

page count 0,0 0,0 0 0,0 0,0 0 0,0 0,0 0 0,0 0,0

2006

Standard manuscript page count

2003 2004 2005

4. List of patents and patent applications

2003:Patents: NonePatent applications: None

2004:Patents: NonePatent applications: None

2005:Patents: NonePatent applications: None

2006:Patents: NonePatent applications: None

5. Supplementary information and/or comments on the scientific output of the

Organisation

Generally continuing positive trend in quantity and particularly in quality (illustrated by IF) of CC publications has been observed. Exceptionally high number of publications in 2004 was due to publishing papers from Symposium contributions.

2006 2005 2004 2003 2002CC publications 39 37 46 37 30Average IF 3,65 2,16 2,18 1,87 1,96Top 10 IF 7,0 3,67 3,73 3,47 2,8

Several breakthrough papers were produced from our Institute two of them concern improvement of healthcare – diagnostic and therapy as a part of top international collaboration:

3 This information is required only from the Organisations of the Section 3 of the Slovak Academy of Sciences.

23

Brouwers FM, Petricoin EF, Ksinantova L, Breza J, Rajapakse V, Ross S, Johann D, Mannelli M, Shulkin BL, Kvetnansky R, Eisenhofer G, Walther MM, Hitt BA, Conrads TP, Veenstra D, Mannion DP, Wall MR, Wolfe GM, Fusaro VA, Liotta LA, Pacak K: Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma. ENDOCRINE-RELATED CANCER 12: 263-272, 2005, IF = 4,597 (2004). Paper specifies patients endangered by metastasic pheochromocytoma. This improvement of diagnostics was discussed in the editorial article of the NATURE CLINICAL PRACTICE ONCOLOGY 9 (2): 439-440, 2005 (Rebeca Orreland: Novel method for distinguishing metastatic and benign pheochromocytoma).

Another paper: Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Sligerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Sovik O, Polak M and Hattersley AT (for the Neonatal Diabetes International Collaborative Group including Gasperikova D and Stanik J): Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N ENGL J MED 355 (5): 467-77, 2006, IF = 44,016 (2005). Paper describes application of the top diagnostic approach resulting in diabetes therapy improvement in neonatal patients.

Importance of both papers has been underlined also by editorials published in parallel in Nat Clin Pract Oncol and N Engl J Med, respectivelly.

Dr. Kvetňanský was invited to write a review on Stress and catecholamines for PHYSIOLOGICAL REVIEWS (IF = 28,7). Paper was submitted and is currently under evaluation.

2. Responses to the scientific output

Table Citations shows specified responses to the scientific outputs; these entries are

then divided by the FTE employees with a university degree (from Tab. Research staff)

for all Organisation at the respective year; finally these entries are divided by the total

salary budget (from Tab. Salary budget).

24

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

No

. / F

TE

No

. / sala

ry b

ud

get

nu

mb

er

avera

ged

nu

mb

er

per

year

av. N

o. / F

TE

av. N

o. / sala

ry b

ud

get

Web of Science 454 12,4 34,0 576 15,5 41,9 564 15,0 38,4 615 16,7 39,0 2212 552,3 14,9 38,4

SCOPUS 37 1,0 2,8 59 1,6 4,3 69 1,8 4,7 62 1,7 3,9 227 56,8 1,5 3,9

OTHERS 10 0,3 0,7 10 0,3 0,7 0 0,0 0,0 18 0,5 1,1 38 9,5 0,3 0,7

in monographs, conf. proceedings and other publications abroad

0 0,0 0,0 0 0,0 0,0 0 0,0 0,0 0 0,0 0,0 0,0 0,0 0,0

in monographs, conf. proceedings and other publications in Slovakia

0 0,0 0,0 0 0,0 0,0 0 0,0 0,0 0 0,0 0,0 0 0,0 0,0 0,0

Citations

total2002 2003 2004 2005

i. List of 10 top-cited publications and number of their citations in the

assessment period

1. SEDLAK J , LINDSAY RH: Estimation of total protein-bound and nonprotein sulfhydryl groups in tissue with ellmans reagent. ANALYT BIOCHEM 25: 192-205, 1968

Cited times: 351

2. SMITH MA, MAKINO S, KVETNANSKY R, POST RM: Stress and Glucocorticoids Affect the Expression of Brain-Derived Neurotrophic Factor and Neurotrophin-3 Messenger-RNAs in the Hippocampus. J NEUROSCI 15 (3): 1768-1777 Part 1, 1995

Cited times: 162

3. BARTANUSZ V , AUBRY JM, PAGLIUSI S, JEZOVA D, BAFFI J, KISS JZ: Stress-induced changes in messenger-RNA levels of n-methyl-d-aspartate and ampa receptor subunits in selected regions of the rat hippocampus and hypothalamus. NEUROSCI 66 (2): 247-252, 1995

Cited times: 41

4. SABBAN EL, KVETNANSKY R: Stress-triggered activation of gene expression in catecholaminergic systems: dynamics of transcriptional events. TRENDS IN NEUROSCI 24 (2): 91-98, 2001

Cited times: 36

5. BARTANUSZ V , JEZOVA D, BERTINI LT, TILDERS FJH, AUBRY JM, KISS JZ: Stress-Induced Increase In Vasopressin And Corticotropin-Releasing Factor Expression In Hypophysiotrophic Paraventricular Neurons. ENDOCRINOL 132 (2): 895-902, 1993

Cited times: 35

25

6. KVETNANSKY R , FUKUHARA K, PACAK K, CIZZA G, GOLDSTEIN DS, KOPIN IJ: Endogenous Glucocorticoids Restrain Catecholamine Synthesis And Release At Rest And During Immobilization Stress In Rats. ENDOCRINOLOGY 133 (3): 1411-1419, 1993

Cited times: 34

7. SMITH MA, MAKINO S, KIM SY, KVETNANSKY R: Stress Increases Brain-Derived Neurotropic Factor Messenger-Ribonucleic-Acid in the Hypothalamus and Pituitary. ENDOCRINOL 136 (9): 3743-3750, 1995

Cited times: 32

8. DUNCKO R, KISS A, SKULTETYOVA I, RUSNAK M, JEZOVA D : Corticotropin-releasing hormone mRNA levels in response to chronic mild stress rise in male but not in female rats while tyrosine hydroxylase mRNA levels decrease in both sexes. PSYCHONEUROENDOCRINOL 26 (1): 77-89, 2001

Cited times: 30

9. KISS A, JEZOVA D , AGUILERA G: Activity of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system during food and water-deprivation in the rat. BRAIN RES 663 (1): 84-92, 1994

Cited times: 30

10. DE GOEIJ DCE, KVETNANSKY R, WITHNALL MH, JEZOVA D, BERKENBOSCH F, TILDERS FLH: Repeated stress-induced activation of corticotropin releasing factor neurons enhanced vasopressin stores and colocalization with corticotropin releasing factor in the median eminence of rats. NEUROENDOCRINOL 53: 150, 1991

Cited times: 27

ii. List of top-cited authors from the Organisation (at most 10 % of the research employees) and their number of citations in the assessment period

Author of top cited paper (over 2 200) from the Institute Jozef Sedlák passed away several years ago. Here is the list of top cited authors working at the Institute. Number citations of papers with the Institute displayed on first page (only WOS + Scopus) without self citations are shown.

1. RNDr. R. Kvetňanský, DrSc. 7862. Prof. PharmDr. D. Ježová, DrSc. 7033. MUDr. M. Vigaš, DrSc. 1894. RNDr. A. Kiss, DrSc. 184

iii. Supplementary information and/or comments on responses to the scientific

output of the Organisation

The list of 10 highly cited papers reflects four important aspects of the scientific work at the Institute, namely a) good tradition in methodological background, b) high level of international collaborations, c) high quality of research based solely on the experimental approaches elaborated in the Institute, and d) involvement of young researchers in high quality research work. The researchers from the Institute are the key authors (first or last) on 8 out of 10 most cited papers.

a) The highest cited paper on the list describes a method developed in the Institute more than 30 years ago. The paper is still highly cited, although its author is no more among us for a long time.

b) Several papers on the list resulted from research in international collaboration, particularly with laboratories in the USA, Switzerland and the Netherlands. In most of them (3, 5, 9, 10), either the experimental part in animals or the analyses of hormones were performed in the Institute.

26

c) The work published in paper N.8 was performed solely by the researchers employed in the Institute. It brought new insights into the pathophysiology of experimental depression. The paper N. 4 is a review article summarizing the experimental work at the Institute and in international collaboration in the field of stress and catecholamines.

d) Three out of ten most cited papers (3, 5, 8) are based on research conducted in the course of PhD studies of two young medical doctors (V. Bartanusz and R. Duncko). Experimental work on one of them (8) had started while the first author was a pregraduate medical student. This demonstrates a high level of education of young scientists at the Institute.

3. Research status of the Organisation in the international and national

context

International/European position of the Organisation

i. List of the most important research activities documenting international

importance of the research performed by the Organisation, incl. major projects

(details of projects should be supplied under Indicator 4). Collective

membership in the international research organisations, in particular within the

European Research Area

2003:

The Institute of Experimental Endocrinology, Slovak Academy of Sciences coordinated and participated in the research of a number of substantial multilateral projects of the international scientific/technical collaboration. The researchers of the institute successfully carried on in research of the project “Centre of Excellence” (Reduction of negative impact of environmental factors on human health), No. ICA1-CT-2000-7008) supported by the European Commission. In this project took part also investigators from the European Union countries (Greece, Germany, Austria) as well as from Hungary. The project consisting of 14 work packages enabled to achieve original results that have been presented during the international scientific symposia and published in prestigious scientific journals (23 papers have been published or accepted for publication, 38 abstracts have been published in 2003).In 2003, the researchers of the institute successfully carried on in research of the project of the 5th Framework Programme of the EC (acronym: VITAGE), Vitamin A, vitamin E and carotenoid status and metabolism during ageing: Functional and nutritional consequences), No. QLK1-CT-1999-0083 supported by the European Commission. The part of the data has been summarized in 3 papers published in prestigious journals and also presented during the 6th VITAGE meeting in France. The researchers of the institute successfully carried on in research of the additional project of the 5th Framework Programme of the EC (acronym: PCBRISK), Evaluating human health risk from low-dose and long-term PCB exposure), No.QRLT-2000-00488 supported by the European Commission. The data has shown that long-lasting contamination of the environment by PCBs is linked with enhanced volume of the thyroid gland, enhanced levels of thyroid hormones in serum and decreased levels TSH in the range of subclinical hypothyreosis. Moreover the environmental pollution with PCB is associated with higher frequency of diabetes and other dysglycemic states in the exposed people. The part of the results have been published (4 papers), in 2003.

In 2003, the researchers of the institute started their investigations in two novel projects of the 5th Framework Programme supported by the European Commission. The fourth one,

27

(acronym: ENDOMET, Dysregulation of endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticizers), No. QLK4-CT-2002-02637 and the fifth one (acronym: DROSDEL) Construction of a new Drosophila duplication collection, No. QLRI-CT-2001-02841. In addition to previously mentioned projects, the researchers of the institute worked on multilateral project supported by the NATO: Genes in Control of Apoptosis during Drosophila metamorphosis (LST.CLG 977559) and the project COST B 17: Fatty acid oxidation and insulin resistance, and 4 international projects based on inter-governmental scientific/technical collaboration.

Active bilateral international projects 5

Active multilateral international projects of the “International scientific/technical collaboration” 22

- Projects of the 5th Framework Programme of the EC 5- Projects of the 6th Framework Programme of the EC 0- Multilateralprojects

(COST, INTAS, EUREKA, ESPIRIT, PHARE, NATO, UNESCO, CERN, IAEA, ESF and others) 2

- Projects based on inter-governmental scientific/technical collaboration 4 - Other Projects 11

2004:

The Institute of Experimental Endocrinology, Slovak Academy of Sciences coordinated and participated in the research of a number of substantial multilateral projects of the international scientific/technical collaboration. The researchers of the institute successfully carried on in the last year research of the project “Centre of Excellence” (Reduction of negative impact of environmental factors on human health), No. ICA1-CT-2000-7008) supported by the European Commission. In this project took part also investigators from the European Union countries (Sweden, Greece, Germany, Austria) as well as from Hungary. During the 27th Endocrine Meeting (30.9.-2.10.2004), the institute organized presentation of the Centre of Excellence activities. Dr. J. Vennekens-Capko from the European Commission (Honorary Member of the Chair) as well as 12 participants from Sweden, Austria, Germany, Czech Republic, Greece, Russia and France took part at the meeting and presented 21 oral lectures and posters. The researchers of the institute successfully carried on in research of the additional project of the 5th Framework Programme of the EC (acronym: PCBRISC), Evaluating human health risk from low-dose and long-term PCB exposure), No.QRLT-2000-00488 supported by the European Commission. More than 2000 volunteers from the pollutant exposed region (East Slovakia) underwent a number of clinical determinations. The data has shown significantly high levels of 15 congeners of polychlorinated biphenyls and hexachlorobenzene in probands from the town Michalovce. In 2004, the researchers of the institute continued their investigations in two projects of the 5th Framework Programme supported by the European Commission. i) the acronym: ENDOMET, Dysregulation of endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticizers, No. QLK4-CT-2002-02637 and ii) the acronym: DROSDEL, Construction of a new Drosophila duplication collection, No. QLRI-CT-2001-02841. In addition to previously mentioned projects, the researchers of the institute worked on multilateral project supported by the NATO: Genes in Control of Apoptosis during Drosophila metamorphosis (LST.CLG 977559) and the project COST B 17: Fatty acid oxidation and insulin resistance, and 4 international projects based on inter-governmental scientific/technical collaboration.

28

Active bilateral international Projects 4

Active multilateral international projects “International scientific/technical collaboration” (MVTS): 22 - Projects of the 5th Framework Programme of the EC 4- Projects of the 6th Framework Programme of the EC 0- Multilateral projects

(COST, INTAS, EUREKA, ESPIRIT, PHARE, NATO, UNESCO, CERN, IAEA, ESF and others) 2

- Projects based on inter-governmental scientific/technical collaboration 5 - Other Projects 112005:

The Institute of Experimental Endocrinology, Slovak Academy of Sciences participated in the research of a number of substantial multilateral projects of the international scientific/technical collaboration. In 2005, the researchers of the institute continued their investigations in one projects of the 5th Framework Programme supported by the European Commission: Dysregulation of endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticizers, No. QLK4-CT-2002-02637 (ENDOMET) In addition, the institute participated at the projects: Insulin Resistance, Obesity and Diabetes Mellitus in the Elderly (COST B17), the USA-Slovakia Collaboration Project: Ethanol and Cell Swelling Induced Peptide Secretion: Intracellular Signalling and Regulation between Laboratory of Neurohumoral Regulations in Bratislava and the Department of Medicine, Oregon Health Sciences, University of Portland, Oregon, USA. The Laboratory of Pharmacological Endocrinology in Bratislava took part at the project: Environmental Influences on Hormone Release during Stress in Humans: Continuation of Previous Common Studies, SK-04-BA-009 within the Austrian-Slovak Collaboration and the project with the institution in Greece, project: Environmental Stimuli and Neuronal Plasticity, CD-2005-14768/16497. Successful bilateral collaborations took place between the Laboratory in the USA and the Laboratory of Diabetes and Nutrition in Bratislava – project: Slovakia PCB Exposures and Early Childhood Development as well as between Laboratory in Bratislava and the Institute of Nuclear Sciences Vinca, Beograd, Serbia and Monte Negro.

Active bilateral international Projects 2

Active multilateral international projects “International scientific/technical collaboration” (MVTS): 20 - Projects of the 5th Framework Programme of the EC 1- Projects of the 6th Framework Programme of the EC 0- Multilateral projects

(COST, INTAS, EUREKA, ESPIRIT, PHARE, NATO, UNESCO, CERN, IAEA, ESF and others) 1

- Projects based on inter-governmental scientific/technical collaboration 7- Other Projects 11 2006:

The Institute of Experimental Endocrinology, Slovak Academy of Sciences participated in the research of a number of substantial multilateral projects of the international scientific/technical collaboration. In 2006, the researchers of the institute continued their investigations in one projects of the 5th Framework Programme supported by the European Commission: Dysregulation of

29

endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticizers, No. QLK4-CT-2002-02637 (ENDOMET) and started to work on two new projects of the 6th Framework Programme supported by the European Commission: Chemical contaminants in the food chain No. FOOD-CT-2004-506319 (acronym: CASCADE, NoE) and the project: The Danubian Biobank Inititative: Towards Information-Based Medicine, No. FP6 – 018822 (SSA). In addition, the institute participated at the investigation on the new international projects: i) Slovak-France project: STEFANIK (No. SK-Fr-02006): Transmembrane interactions in cellular signalling, ii) the Greece-Slovak project (No. CD-2005-14768/16497): Environmental stimuli and neuronal plasticity and iii) the Austrian-Slovakian project (No. SK-05/06-BA-007): Evaluation of stress, brain and cardiovascular system. New bilateral project (The Netherlands and Slovakia) focuses on the effects of the vagal nerve stimulation on tumor development and progression.

Active bilateral international Projects 2

Active multilateral international projects “International scientific/technical collaboration” (MVTS): 17 - Projects of the 5th Framework Programme of the EC 1- Projects of the 6th Framework Programme of the EC 2- Multilateral projects

(COST, INTAS, EUREKA, ESPIRIT, PHARE, NATO, UNESCO, CERN, IAEA, ESF and others) 0

- Projects based on inter-governmental scientific/technical collaboration 4- Other Projects 10 ii. List of international conferences (co-) organised by the Organisation

2003:RNDr. Richard Kvetňanský, DrSc.EIGHTH SYMPOSIUM ON CATECHOLAMINES AND OTHER NEUROTRANSMITTERS IN STRESS, Smolenice (June 28th-July 3rd, 2003) For more information please, see http://www.stress.sav.sk

2004:Doc. PharmDr. Daniela Ježová, DrSc.PRESENTATION OF THE CENTRE OF EXCELLENCE SUPPORTED BY EC, XXVII. Days of Endocrinology, Piešťany, 30.9.-2.10.2004,

2005:Ing. Štefan Zorad, CSc.IXth BIOLOGICALLY ACTIVE PEPTIDES Conference, Prague, Czech Republic, 20.-22.4.2005

2006:Prof. MUDr. Iwar Klimeš, DrSc.- XVI. DIABETOLOGICAL DAYS, 1.-3.6.2006. - ENDOCRINOLOGICAL DAYS, 21.-23.9.2006. - Second ESE Postgradual Course on Clinical Endocrinology, Košice, Slovakia, 12.-

14.10.2006.

iii. List of international journals edited/published by the Organisation

30

2003:[1] ENDOCRINE REGULATIONS

2004:[1] ENDOCRINE REGULATIONS

2005:[1] ENDOCRINE REGULATIONS

2006:[1] ENDOCRINE REGULATIONS

iv. List of edited proceedings from international scientific conferences and other

proceedings

2004:[1] Richard Kvetňanský, special issue editor of the Annals NY Acad Sci 1018, June 2004:

Stress: Current Neuroendocrine and Genetic Approaches (Eighth Symposium On Catecholamines and other Neurotransmitters in Stress, Smolenice 2003

2006:[1] Vladimir Štrbák, special issue editor of Cellular and Molecular Neurobiology, 26:

November 2006: Proceedings of the 5th International Symposium on Experimental and Clinical Neurobiology, High Tatras, Slovakia, September 2005,

National position of the Organisation

The role of the Institute in the field is reflected by editorial role of scientists (eds. Klimeš, Langer) in editing of the textbook Basic and Clinical Endocrinology 2004 (co-authors: Brtko, Gašperíková, Hučková, Ježová, Klimeš, Langer, Macho, Šeboková, Vigaš) for postgraduate students.

i. List of selected most important national projects (Centres of Excellence,

National Reference Laboratories, Agency for the Promotion of Research and

Development (APVV/APVT), National Research Programmes, Scientific Grant

Agency of the Slovak Academy of Sciences and the Ministry of Education

(VEGA), and others)

Centres of Excellence:

2006: Centrum of Excellence for the research of neuroendocrine mechanisms in the pathogenesis of serious diseases (acronym CENDO)

APVT:

2003: 1) APVT 21-008602 - Interaction of central and local hormonal and immune factors in

the pathogenesis and development of rheumatoid arthritis

31

2) APVT 20-016002 - Immobilized biological systems: Regulation of transport of nanoscale bioactive substances through well-defined polymer membranes in biotechnology and biomedicine

2004: 1) APVT 21-008602 - Interaction of central and local hormonal and immune factors in

the pathogenesis and development of rheumatoid arthritis

2) APVT 51-040602 - Hormonal regulation of gene expression for enzymes of lipid metabolism in the adipose tissue of obese and insulin resistant subjects

3) APVT 51-027402 - Genes involved in programmed cell death

4) APVT 20-016002 - Immobilized biological systems: Regulation of transport of nanoscale bioactive substances through well-defined polymer membranes in biotechnology and biomedicine

2005: 1) APVT 51-027402 - Genes involved in programmed cell death in Drosophila

2) APVV 51-040602 - Hormonal regulation of gene expression for enzymes of lipid metabolism in the adipose tissue of obese and insulin resistant subjects

3) APVT 21-008602 - Interaction of central and local hormonal and immune factors in the pathogenesis and development of rheumatoid arthritis

4) APVT 20-016002 - Immobilized biological systems: Regulation of transport of nanoscale bioactive substances through well-defined polymer membranes in biotechnology and biomedicine

2006: 1) APVT 51-027402 - Genes involved in programmed cell death in Drosophila

2) APVT 51-040602 - Hormonal regulation of gene expression for enzymes of lipid metabolism in the adipose tissue of obese and insulin resistant subjects

3) LPP-0194-06 - Education of young specialists in the field of the neurobiological basis of mental disorders

4) APVV 51-017905 - Molecular mechanisms of new drugs influencing oxidative stress – important ethiopathogenetic factor of numerous diseases

5) APVV-51-014205 - DNA analysis of monogenic forms of diabetes in Slovakia

National Research Program:

2003: 2003 SP 51/028 08 00/028 08 02 - Genomics of cardiovascular diseases for healthier human population

2004:

32

2003 SP 51/028 08 00/028 08 02-2004 - Genomics of cardiovascular diseases for healthier human population

2005: 2003 SP 51/028 08 00/028 08 02-2005 - Genomics of cardiovascular diseases for healthier human population

National Diabetes Program:

2003: Screening of MODY and MIDD

2004: Screening of DM-2, MODY-3 and MIDD

Projects supported by Slovak Ministry of Health:

2006: 1) MZ 2005/15-NEDU-01 - Introduction of DNA diagnostics and the screening of monogenic forms of diabetes in Slovakia

2) MZ 2005/20- NURCH-04 - The effect of chronic inflammation on metabolism in rheumatic diseases

Projects supported by European Social Fund:

2005: 1) 13120200056 - Health of inhabitants of Bratislava region – contribution to better

coping with stress based on results of top research

2) 13120200067 - Positron emission tomography for small laboratory animals, introduction of the method in research and evaluation of new drugs in Centre of Excellence of the EU

2006: 1) 13120200056 - Health of inhabitants of Bratislava region – contribution to better

coping with stress based on results of top research

2) 13120200067 - Positron emission tomography for small laboratory animals, introduction of the method in research and evaluation of new drugs in Centre of Excellence of the EU

VEGA:

2003: 1) 2/2090/23 - Studies of the regulation of gene expression of enzymes of

catecholaminergic system and their modulation by transcription factors in mammals due to the stress

2) 2/2007/23 - Simulation of stress states occurring in daily life: type of stress stimuli and neuroendocrine function

33

3) 2/3150/23 - The role of neuroendocrine mechanisms in the insulin resistance and hypertension in human

4) 2/3190/23 - Contribution to revealing the role of local renin – angiotensin systems in adipose tissue, spleen, lymphocytes and mammary gland carcinoma

5) 2/1098/23 - The role of transmembrane segment of membrane receptors in the mechanism of their effect

6) 2/3191/23 - Traditional and unconventional mechanisms of regulation of peptide secretion

7) 2/3099/23 - Endocrine disruptors /polychlorinated biphenyls and pesticides/ and frequency of diabetes and markers of mammary gland cancer in inhabitants of polluted areas

8) 2/2070/23 - In vivo transfection of DNA vaccines in relation to biological effects of retinoic acids in normal and neoplastic tissue of mammary gland in rat

9) 2/3052/23 - Xenoestrogens related disorders in female reproductive system

10) 2/3025/23 - Molecular-genetic analysis of the function and expression of hormonally responsive malate dehydrogenases in Drosophila melanogaster

11) 1/8287/23 - Offspring of diabetic mothers in adolescence

2004: 1) 2/2007/23 - Simulation of stress states occurring in daily life: type of stress stimuli

and neuroendocrine function

2) 2/2070/22 - In vivo transfection of DNA vaccines in relation to biological effects of retinoic acids in normal and neoplastic tissue of mammary gland in rat

3) 2/2090/24 - Studies of the regulation of gene expression of enzymes of catecholaminergic system and their modulation by transcription factors in mammals due to the stress

4) 2/3025/23 - Molecular-genetic analysis of the function and expression of hormonally responsive malate dehydrogenases in Drosophila melanogaster

5) 2/3052/23 - Xenoestrogens related disorders in female reproductive system

6) 2/3099/23 - Endocrine disruptors /polychlorinated biphenyls and pesticides/ and frequency of diabetes and markers of mammary gland cancer in inhabitants of polluted areas

7) 2/3150/23 - The role of neuroendocrine mechanisms in the insulin resistance and hypertension in human

8) 2/3190/23 - Contribution to revealing the role of local renin – angiotensin systems in adipose tissue, spleen, lymphocytes and mammary gland carcinoma

34

9) 2/3191/23 - Traditional and unconventional mechanisms of regulation of peptide secretion

10) 2/4030/4 - Mechanism of protective and harmful effect of alcohol on hormonally controlled metabolism of adipose tissue

11) 2/4128/4 - Development of experimental arthritis in rats under different nutritional conditions: the involvement of leptin

2005: 1) 2/5017/5 - Character, function and role of transcription factors inducible by

biologically active hydrophobic molecules in rat mammary gland

2) 2/3025/23 - Molecular-genetic analysis of the function and expression of hormonally responsive malate dehydrogenases in Drosophila melanogaster

3) 2/4030/4 - Mechanism of protective and harmful effect of alcohol on hormonally controlled metabolism of adipose tissue

4) 2/5064/5 - Neuroendocrine mechanisms in relation to mental state and to the effects of psychotropic drugs

5) 2/4128/4 - Development of experimental arthritis in rats under different nutritional conditions: the involvement of leptin

6) 2/3099/23 - Endocrine disruptors /polychlorinated biphenyls and pesticides/ and frequency of diabetes and markers of mammary gland cancer in inhabitants of polluted areas

7) 2/5125/25 - Transcriptional mechanisms of stress-induced changes in gene expression of catecholamine biosynthetic enzymes and their receptors

8) 2/5090/25 - Study on structure – activity relationship of insulin analogs modified in the C-terminus of the insulin B-chain

9) 2/3052/23 - Xenoestrogens related disorders in female reproductive system

10) 2/3191/23 - Traditional and unconventional mechanisms of regulation of peptide secretion

11) 2/3150/24 - The role of neuroendocrine mechanisms in the insulin resistance and hypertension in human

12) 2/3190/23 - Contribution to revealing the role of local renin – angiotensin systems in adipose tissue, spleen, lymphocytes and mammary gland carcinoma

2006: 1) 2/5017/5 - Character, function, and role of transcription factors inducible by

biologically active hydrophobic molecules in rat mammary gland

2) 2/4030/26 - Mechanism of protective and harmful effect of alcohol on hormonally controlled metabolism of adipose tissue

35

3) 1/1185/26 - Secondary metabolites of selected plants species influencing apoptosis

4) 2/5064/5 - Neuroendocrine mechanisms in relation to mental state and the effects of psychotropic drugs

5) 2/4128/4 - Development of experimental arthritis in rats under different nutritionalconditions: role of leptin

6) 2/5125/26 - Transcriptional mechanisms of stress-induced changes in gene expression of catecholamine biosynthetic enzymes and their receptors

7) 2/6171/26 - Effect of binary mixtures of xenoestrogens on ovarian intrafollicular processes

8) 2/6158/26 - Novel signaling pathway for swelling-induced hormone secretion

9) 2/6157/27 - Adrenal gland and sympathetic nervous system in the pathogenesis of rheumatic diseases

10) 2/5090/25 - Study on structure – activity relationship of insulin analogs modified in the C-terminus of the insulin B-chain

ii. List of national scientific conferences (co)-organised by the Organisation

.1/ 2nd Slovak Obesitology Days, Nimnica Spa 2003.

2/ 22nd Seminar of Clinical Endocrinology, Trenčianske Teplice 2004.

3/ 4th Slovak Obesitology Days, Nimnica Spa 2005.

4/ 5th Slovak Obesitology Days, Nimnica Spa 2006.

iii. List of national journals published by the Organisation

None

iv. List of edited proceedings of national scientific conferences/events

None

International/European position of the individual researchers

i. List of invited/keynote presentations at international conferences, documented

by an invitation letter or programme

2003:

JEŽOVÁ D.: Bipolar disorder, stress and mood stabilizers. Symposium on Bipolar Disorder, Bratislava, Slovakia, 4.-6.4.2003.

JEŽOVÁ D.: Perinatal and postnatal stress in relation to psychic alienation. Symposium on therapeutical algorithms in pedopsychiatrics, Bratislava, Slovakia, 16.4.2003.

36

JEŽOVÁ D.: Psychotropic drugs and the stress response. IX. Psychopharmacological symposium, Smolenice, Slovakia, 17.-19.11.2003.

JEŽOVÁ D.: Stress hormones and effects of psychotropic drugs in relation to neuroplasticity. 11th International symposium. New frontiers of neurochemistry and neurophysics on diagnosis and treatment of neurological diseases. Martin, Slovakia, 4.-7.12.2003.

JEŽOVÁ D., DUNČKO R., SMRIGA M., MORINAGA Y., MONČEK F., MAKATSORI A.: Psychosocial stress, anxiety and dietary amino-acids in healthy men. 8th Symposium on Catecholamines and Other Neurotransmitters in Stress. Smolenice, 28.6.-3.7.2003.

JEŽOVÁ D., DUNČKO R., MONČEK F.: Role of neuroendocrine factors in the action of psychotropic drugs. 45th Czech and Slovak Psychopharmacological Conference, Lázně Jeseník, Czech Republic, 3-7.1.2003.

JEŽOVÁ D., MAKATSORI A., SCHWENDT M., MLYNÁRIK M.: Hormonal adaptation in stress and possibilities of its pharmacological modulation. 45 th Czech and Slovak Psychopharmacological Conference, Lázně Jeseník, Czech Republic, 3-7.1.2003.

KLIMEŠ I.: Current possibilities of the prevention of diabetes II. XIII. Diabetological Days and the Symposium MERCK, Liptovský Mikuláš, Slovakia, 21.-23.5.2003.

KLIMEŠ I.: Pathophysiology of the metabolic syndrome. II. Congress of the Slovak Gerontology and Geriatric Society, Tále, Slovakia, 10.9.2003.

KLIMEŠ I. ŠEBOKOVÁ E.: Metabolic syndrome and obesity epidemy. Bad Tatzmansdorf, Austria, 7.6.2003.

KLIMEŠ I.: Current possibilities of the prevention of diabetes II. 26 th Endocrinological Days, Liberec, Czech Republic, 2.-4.10.2003.

KVETŇANSKÝ R.: Stressor specificity and effects of prior experience on catecholamines and their biosynthetic enzymes. XXIV. Meeting of International Society for Psychoneuroendocrinology, New York City, USA, 7-9.9.2003.

KVETŇANSKÝ R.: Catecholamine metabolism and microgravity. 5th European Federation of Autonomic societies, Toulouse, France, 22.-24.5.2003.

KVETŇANSKÝ R., MIČUTKOVÁ L., PALKOVITS M., SABBAN E.L., KRIŽANOVÁ O.: Regulation of cardiac phenylethanolamine N-methyltransferase gene expression in rat during stress. 8th Symposium on Catecholamines and Other Neurotransmitters in Stress, Smolenice, Slovakia, 28.6.-3.7.2003.

KVETŇANSKÝ R., MIČUTKOVÁ L., RYCHKOVÁ N., KUBOVČÁKOVÁ L., MRAVEC B., FILIPENKO M., SABBAN E.L., KRIŽANOVÁ O.: Quantitative evaluation of catecholamine enzymes gene expression in adrenal medulla and sympathetic ganglia of stressed rats. 8th Symposium on Catecholamines and Other Neurotransmitters in Stress, Smolenice, Slovakia, 28.6.-3.7.2003.

MACHO L., KOŠKA J., KŠINANTOVÁ L., VIGAŠ M., BLAŽÍČEK P., NOSKOV V.B., GRIGORIEV A.I., PACÁK K., KVETŇANSKÝ R.: Effects of real and

37

simulated microgravity on responses of sympathoadrenal system to various stress stimuli. The 8th Symposium on Catecholamines and other Neurotransmitters in Stress, Smolenice, Slovakia, 28.6.-3.7.2003.

ŠEBOKOVÁ E., KLIMEŠ I.: Metabolic syndrome – new epidemy. VIII. Congress of the Slovak Cardiological Society with International Participation, Bratislava, Slovakia, 9.-11.10.2003.

ŠEBOKOVÁ E., KLIMEŠ I.: Metabolic syndrome – the role of fatty tissue. X. Obesity Conference, Olomouc, Czech Republic 16.-18.10.2003.

ŠEBOKOVÁ E., KLIMEŠ I.: Metabolic syndrome – new epidemy. 26. Endocrinological Days, Liberec, Czech Republic, 2.-4.10.2003.

ŠEBOKOVÁ, E.: Metabolic syndrome – new epidemy. XIII. Diabetological Days, Liptovský Mikuláš, Slovakia, 21.-23.5.2003.

ŠTRBÁK V., BENICKÝ J., GREER, S.E., BAČOVÁ Z., NAJVIRTOVÁ M., GREER M.A.: Cell swelling-induced exocytotic secretion. 3rd FEPS Congress, Nice, 28.6.-2.7. 2003.

ŠTRBÁK V., BENICKÝ J., GREER S.E., BAČOVÁ Z., NAJVIRTOVÁ M., GREER M.A.: Cell swelling-induced peptide hormone secretion. International Symposium Cell Volume & Signal Transduction, Dayton, Ohio, 20.-24.9.2003.

ŠTRBÁK V.: Cell volume regulation and peptide secretion. Risk factors and health: from molecule to the scientific basis of prevention, Belgrade/Zrenjanin, 7.-9.11.2003. International conference organized by Serbian Physiological Society under Auspices of Federation of European Physiological Societies, International Society of Pathophysiology, International Union of Physiological Sciences

2004:

JEŽOVÁ D., MAKATSORI A., DUNČKO R., SCHWENDT M.: Glutamate in relation to stress and drug action. 12th AEP Congress, Geneva, Switzerland, 14.-18.4.2004

JEŽOVÁ D.: Genital differences in stress reaction and during the effects of antidepressives. Symposium of the Biological aspects of insanity. Slovak Psychiatrics Congress, Spišská Nová Ves, Slovakia, 9.-12.6.2004

JEŽOVÁ D.: Reality and dream about the role of stress hormones during anxiety and in depression. II. Czech and Slovak Neuropsychiatry’s Symposium, Český Krumlov, Czech Republic, 23.–25.9.2004

JEŽOVÁ D.: Hormones and their relationship to psychic functions. Charvát Lecture XXVII. Endocrinological Days with the International Participation, Piešťany, Slovakia, 30.9.-2.10.2004

KLIMEŠ I., RÁDIKOVÁ Ž., KOŠKA J., KŠINANTOVÁ L., IMRICH R., KOČAN A., HUČKOVÁ M., PETRÍK J., JURSA S., WIMMEROVÁ S., LANGER P., TRNOVEC T., HOWARD B.V., ŠEBOKOVÁ E.: Diabetes and other dysglycemias in subjects chronically exposed to polychlorinated biphenyls (PCB). 32. Jahrestagung der

38

Österreichischen Diabetes Gesellschaft, Diabetes als gesamtmedizinische Herausforderung, Baden, Austria, 2.-4.12.2004

KVETŇANSKÝ R.: Effect of space flight and head-down bed rest on neuroendocrine response to metabolic stress in physically fit subject. International Congress of Gravitation Physiology, Moscow, Russia, 6-11. 6. 2004

KVETŇANSKÝ R.: Responses to stress: habituation and dishabituation. 5th World Congress on Stress, London, UK, 18.6.2004

RÁDIKOVÁ Ž., KOŠKA J., KŠINANTOVÁ L., IMRICH R., KOČAN A., PETRÍK J., HUČKOVÁ M., CHOVANCOVÁ J., DROBNÁ B., JURSA S., WIMMEROVÁ S., WSOLOVÁ L., LANGER P., TRNOVEC T., ŠEBOKOVÁ E., KLIMEŠ I.: Increased prevalence of diabetes mellitus and other dysglycemias in a population chronically exposed to polychlorinated biphenyls and other persistent organochlorine pollutants. PCB Workshop, Champaign, IL, USA, 13.-15.6.2004

ŠTRBÁK V.: Cell volume regulation: Relation to ischemia and cell proliferation. Inflammation 2004, First Romanian Symposium with International Participation, Sambata de Sus, Romania, 20.-23.4.2004.

2005:

BRTKO J.: Nuclear thyroid hormone and retinoic acid receptors: Research in the past, present, and in the future. The 1st Annual Cascade Meeting, Orvieto, Italy, 20.-23.1.2005

BRTKO J.: Retinoid nuclear receptors and their role in therapy of selected malignancies. 10th Interdisciplinary Czech and Slovak Toxicological Conference, TOXCON, Olomouc, Czech Republic, 14.-16.9.2005

BRTKO J.: Nuclear receptors of retinoids and rexinoids and their role in chemoprevention and therapy of selected malignancies. XXVIII. Endocrinological Days with the International Participation, Olomouc, Czech Republic, 20.-22. 10.2005

FARKAŠ R.: Identification of target genes of steroid receptors: A complex genomic response in Drosophila; XXVIII. Endocrinological Days with the International Participation, Olomouc, Czech Republic, 20.-22. 10.2005

FICKOVÁ M.: Apoptic effects of selected plant metabolites. 10th Workshop of the Natural Pharmaceutical Preparations, Ľubovianske kúpele, Slovakia, 5.-7.9.2005

IMRICH R.: Hypoglycaemia and the sympathetic nervous system. Third International Conference on: Neuroendocrine immune basis of the rheumatic diseases, Genova, Italy, 2005

JEŽOVÁ D., VIGAŠ M., MLYNÁRIK M.: Development of drug addiction and

hormones. 47th Czech and Slovak Pharmacological Conference, Láznĕ Jeseník, Czech Republic, 5.–9.1.2005

JEŽOVÁ D.: Neuroendocrine consequences of increasing neural plasticity by enriched environment. 5th International Symposium on Experimental and Clinical Neurobiology, Stará Lesná, Slovakia, 19.-22.9.2005

39

JEŽOVÁ D.: Stress, hormones and depression. 12th Czech and Slovak Psychiatrics Congress, Vysoké Tatry, Slovakia, 1.–4.12.2005

JEŽOVÁ D.: Would it be advantageous to decrease or increase of the neuroendocrine activation during stress ? 123th Institute seminar, Psychiatrics Centre, Prague, Czech republic, 1.3.2005

JEŽOVÁ D.: Stress hormone release in relation to depression and anxiety. Neurobiological Colloquium, University of Regensburg, Germany, 28.4.2005

KLIMEŠ I.: Erfahrungen mit der molekularen Diagnostik von MODY-3 und MODY-2 in der Slowakei. 20. Symposium der Főderation der Internationalen Donau-Symposia, Wiesbaden, Germany, 27.-29.10.2005

KLIMEŠ I., RÁDIKOVÁ Ž., KOŠKA J., HUČKOVÁ M., KOČAN A., KŠINANTOVÁ L., IMRICH R., PETRÍK J., JURSA S., GAŠPERÍKOVÁ D., LANGER P., TRNOVEC T., ŠEBOKOVÁ E.: Prevalence of diabetes mellitus and other stages of impaired glucose homeostasis in subjects with longterm exposure to organochlorine compounds. A satellite Symposium of the 1st International Congress on Prediabetes and the Metabolic Syndrome, Dresden, Germany, 16.3.–8.4.2005.

KVETŇANSKÝ R.: Catecholaminergic systems in stress: molecular genetic approaches. 41st Annual meeting of Argentina Society for Biochemistry and Molecular Biology Research, Pinamar, Buenos Aires, Argentina, 3.-6.12.2005.

KVETŇANSKÝ R., KOŠKA J., DRONJAK S., NOSKOV V.B., MACHO L., VIGAŠ M., GRIGORIEV A.I., PACÁK K., SABBAN E.L.: Weightlessness, stressor specificity and effect of prior experience on catecholamines and gene expression of enzymes involved in their synthesis. 15th Human in Space Symposium, Graz, Austria, 22.-26.5.2005.

KVETŇANSKÝ R.: Sympathoadrenal system activity in acute and chronic stress situations. Clinical Medicine Congress, Incheba, Bratislava, Slovakia, 18.5.2005

ŠTRBÁK V.: TRH and Cardiovascular system. 49th Medical Students Congress, Kotor, Monte Negro, 5.5.2005

ŠTRBÁK V.: Cell swelling induced peptide hormone secretion. Le 72éme Congrés de la Société de Physiologie, Rennes, France, 27.-29.6. 2005

ŠTRBÁK V.: Unique signaling pathway for swelling induced hormone secretion. (Molecular, cellular and integrative basis of health, disease and therapy) The first congress of Physiological Sciences of Serbia and Montenegro with International participation, Belgrade, Serbia, 9.-12.11.2005.

UKROPEC J., ANUNCIADO R.V., KOZAK L.P.: Novel thermogenetic mechanisms independent from UPC 1 could play a role in an increase energy output and for obesity treatment. Physiological Institute, Czech Academy of Sciences, Prague, Czech Republic, 10.12.2005.

40

2006: BENICKÝ J.: Reversal of cerebrovascular inflammation by angiotensin II AT1

receptor antagonists. Gordon Conference Angiotensin, Aussois, France, 10.–15.9.2006.

BRTKO, J.: Mechanisms of the intracellular effects of thyroid hormones. XXIII. Endocrinological Clinical Days, Banská Bystrica, Slovakia, 24.-25.3.2006

BRTKO J., MACEJOVÁ D., ONDKOVÁ S., THALHAMER J.: Retinoic acid-inducible transcription factors and their role in therapy of selected malignant diseases. XX. Biochemical Congress, (40 min. “Key lecture”), Piešťany, Slovakia, 12.-16.9.2006.

BRTKO J.: Biotechnologies and selected products. XXIX. Endocrinological Days with the International Participation, Ružomberok, Slovakia, 21.-23.9.2006.

GAŠPERÍKOVÁ D.: Inflammatory adipocytokines in obesity and growth hormone deficiency. Adipose tissue and inflammation. Workshop at the German Diabetes Center, Dusseldorf, Dusseldorf, Germany, 24.10.2006.

GAŠPERÍKOVÁ D., PENESOVÁ A., ŠKOPKOVÁ M., VLČEK M., RÁDIKOVÁ Ž., BELAN V., KOŠKA J., ŠEBOKOVÁ E., KLIMEŠ I.: Expression of selected adipocytokines in obese probands with metabolic syndrome. XIV. Symposium: Novel Trends in Atherosclerosis Prevention, Bratislava, Slovakia, 16.2.2006.

JEŽOVÁ D.: Stress hormones and anxiety disorders. European College of Neuropsychopharmacology, ECNP - Educational Workshop, Smolenice, Slovakia, 6.- 8.4. 2006.

JEŽOVÁ D.: Hormones involved in stress, cardiovascular function and mood disorders. 4th ISPNE Regional Congress for Eastern and Central Europe “Stress and psychoendocrine changes across the life cycles”, Vilnius, Lithuania, 15.-17.6.2006.

JEŽOVÁ D.: Psychosocial stress in humans: Anxiety and drug effects. XXV. CINP Congress, Chicago, USA, 6.-13.7.2006.

JEŽOVÁ D.: Neuroendocrinology of affective and anxiety disorders. ESF EMRC Exploratory Workshop „Links between visceral dysfunction and affective disorders“. Graz, Schloss St. Martin, Austria, 31.8 – 3.9.2006.

JEŽOVÁ D.: Antiepileptics as thymoprofylactics and glutamate. 48th Czech and Slovak Psychopharmacological Conference, Láznĕ Jeseník, Czech Republic, 4. – 8.1.2006.

JEŽOVÁ D.: Pharmacology of sex hormones. 48th Czech and Slovak Psychopharmacological Conference, Láznĕ Jeseník, Czech Republic, 4. – 8.1.2006.

KLIMEŠ I.: Endocrinology of the adipose tissue. 2nd ESE Postgraduate Course in Clinical Endocrinology, Košice, Slovakia, 12.-14.10.2006

41

KVETŇANSKÝ R.: Catecholamines in stress: from gene expression of biosynthetic enzymes to metabolic degradation. XX. Biochemical Congress, Piešťany, Slovakia, 12.-16.9.2006.

KVETŇANSKÝ R.: Molecular genetics of sympathoadrenal system in stress. 5th International Congress of Pathophysiology, Beijing, China, 28.6.-1.7.2006.

RÁDIKOVÁ Ž., TAJTÁKOVÁ M., KOČAN A., TRNOVEC T., ŠEBOKOVA E., KLIMEŠ I., LANGER P.: Environmental Nitrates and Polychlorinated Biphenyls (PCBs): Evaluation of Effects on the Thyroid. American Thyroid Association Spring Meeting: Thyroid health and the environment – threats and effects, Washington DC, USA, 2006.

ŠTRBÁK V., BAČOVÁ Z., OREČNÁ M., HAFKO R.: Cell swelling-induced peptide hormone secretion, pathophysiological implications. 5th International Congress of Pathophysiology, Beijing, China, Symposium Cell Volume, physiological and pathophysiological aspects, 28.6.-1.7.2006.

ŠTRBÁK V.: Swelling-induced secretion: general ancient response of cells to hypotonicity. UNESCO seminar Mechanisms of mechanotransduction in living cells, Yerevan, Armenia, 1.-4. 8. 2006

UKROPEC J., ŠKOPKOVÁ M., PENESOVÁ A., VLČEK M., RÁDIKOVÁ Ž., KOŠKA J., SELL H., ECKEL J., PAYER J., KLIMEŠ I., GAŠPERÍKOVÁ D.: Adipose tissue cytokine expression profile in the growth hormone deficiency: preliminary results of the protein array analysis. Workshop at the German Diabetes Center, Dusseldorf, Germany, 24.10.2006

UKROPEC J, ANUNCIADO RV, KOZAK LP: Molecular mechanisms of molecular thermogenesis in Ucp1–/– mice. Boston University Medical Center, MA, USA, 12. 6. 2006

ZÓRAD Š: The role of circulating factors and adipose tissue in brain endothelial function and inflammation. Gordon Conference Angiotensin, Aussois, France, 10.-15.9.2006.

ii. List of employees who served as members of the organising and/or programme

committees for international conferences

2003:

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Executive Secretary of the Eighth Symposium on Catecholamines and Other

Neurotransmitters in Stress, Smolenice, Slovakia, 28.6.-3.7.2003- Member of the Organizing and Programme Committee of the 45 th Czech and Slovak

Psychopharmacology Conference, Lázně Jeseník, Czech Republic, 3.-7.5.2003

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Chairman of the Programme Committee of the XIII. Diabetological Days with the

International Participation in Liptovský Mikuláš, Slovakia 21.-23.5.2003 - Member of the Programme Committee of the XXIX. Diabetelogy Days, Luhačovice,

Czech Republic, 24.-26.4.2003- Member of the Programme Committee of the XXVI. Endocrinological Days, Liberec,

Czech Republic, 2.-4.10.2003

42

RNDr. R. Kvetňanský, DrSc.- President of the Eighth Symposium on Catecholamines and Other Neurotransmitters in

Stress, Smolenice, Smolenice, Slovakia, 28.6.-3.7.2003

MUDr. V. Štrbák, DrSc.- Member of the International Advisory Committee, 3rd Congress of Federation of European

Physiological Societies, Nice, France, 28.6.-2.7.2003- Member of the International Program Committee medzinárodnej konferencie Risk factors

and health: from molecule to the scientific basis of prevention, Belgrade/Zrenjanin, Serbia, 7.-9.11.2003

2004:

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Member of the Organizing and Programme Committee of the 46th. Czech and Slovak

Psychopharmacological Conference, Lázně Jeseník, Czech Republic, 7.–11.1.2004- The Chair of the Symposium Diabetes mellitus during ontogenesis within the XIV.

Symposium of the Polish Society for Children Endocrinology, Wisla, Poland, 15.–17.10. 2004

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Chairman of the Programme Committee of the 27th Endocrinological Days with the

International Participation, Piešťany, Slovak Republic, 2.10.2004

RNDr. R. Kvetňanský, DrSc.- Member of the Organizing Committee of the 5th World Congress on Stress, London, UK,

18.-20.6.2004- Member of the Organizing Committee of the 25 th Annual International Gravitational

Physiology Meeting, Moscow, Russia, 6.-11.6.2004

2005:

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Member of Honorary Presidium, The 12th Conference of Biological Psychiatrics,

Luhačovice, Czech Republic, 15. – 18.6.2005- Coordinator of the Symposium CINP Regional Central/Eastern European Symposium

„Neurobiology of stress and anxiety“ held during the 12th Conference of Biological Psychiatrics, Luhačovice, Czech Republic, 15. – 18.6.2005

- Member of the Scientific Advisory Board, 5th International Symposium on Experimental and Clinical Neurobiology, Stará Lesná, Slovakia, 19.-22.9.2005

Prof. MUDr. I. Klimeš, DrSc.- Member of the XV. Diabetological Days with the International Participation, Košice,

Slovakia, 2.-4. 6.2005- Member of the Programme Committee of the XXVIII. Endocrinological Days with the

International Participation, Olomouc, Czech Republic, 20.-22.10.2005

RNDr. R. Kvetňanský, DrSc.- Member of the Organizing Committee of the 6th International Congress of Neuro-

Immuno-Modulation, Athens, Greece, 25.9.-28.9. 2005. - Member of the Organizing Committee of the 9th European Symposium on Life Sciences

Research in Space and 26th Annual International Gravitational Physiology Meeting, Cologne, Germany, 26.6.-1.7. 2005.

43

- Member of the Organizing Committee of the 15th Human in Space Symposium, Graz, Austria, 22.6.-26.6. 2005.

MUDr. Vladimír Štrbák, DrSc.- President of the Programme Committee of the 81th Physiological Days, Czech and

Slovak Physiological Societies, Košice, Slovakia, 2.-4.2.2005.- Member of the Local Organizing Committee, Advances in cardiology research, Molecular

and Genetic Basis of Cardiovascular Diseases, International Symposium, Smolenice Castle, Slovakia, 13.-16.6.2005.

- Member of the International Advisory Board, MOLECULAR, CELLULAR AND INTEGRATIVE BASIS OF HEALTH, DISEASE AND THERAPY, The first congress of Physiological Sciences of Serbia and Montenegro with International participation, Belgrade, November 9.-12.11.2005

Ing. Š. Zorad, CSc.- Member of the Organizing Committee of the Biologically Active Peptides Conference, 20

– 22.4.2005, Prague, Czech Republic

2006:

RNDr. Mária Ficková, CSc.- Member of the Local Organizing Committee of the XVI. Diabetological Days with the

International Participation, Bratislava, Slovakia, 1.-3.6.2006.

Mgr. Daniela Gašperíková, CSc.- Vice-president of the Organizing Committee of XVI. Diabetological Days with the

International Participation, Bratislava, Slovakia, 1.-3.6.2006.

Prof. PharmDr. Daniela Ježová, DrSc.- Member of the Programme Committee of the 11th Meeting of the Czech and Slovak

Neurochemical Society, Martin, Slovakia, 5.- 7.9.2006.- Member of the International Scientific Committee of the Central/East European CINP

Regional Meeting, Collegium Internationale Neuro-Psychopharmagologicum, Tallinn, Estonia, 5.-7. 10.2006

RNDr. Alexander Kiss, DrSc. - Member of the Local Organizing Committee of the XVI. Diabetological Days with the

International Participation, Bratislava, Slovakia, 1.-3.6.2006.

Prof. MUDr. Iwar Klimeš, DrSc. - President of the Congress and President of the Organizing and Programme Committee

of the XVI. Diabetological Days with the International Participation, 1.-3.6.2006. - President of the Organizing and Programme Committee of the EndocrinologIcal Days

with the International Participation, 21.-23.9.2006. - President of the Course and President of the Organizing and Programme Committee

of the Second ESE Postgradual Course on Clinical Endocrinology, Košice, Slovakia, 12.-14.10.2006.

RNDr. Richard Kvetňanský, DrSc.- Member of the Programme Committee of the 37th Annual ISPNE Conference, Leiden,

The Netherlands, 23 - 26.8.2006. - Member of the Programme Committee of the 11th Meeting of the Czech and Slovak

Neurochemical Society, Martin, Slovak Republic, 6.-10.9.2006.

44

Mgr. Eliška Pravdová- Member of the Local Organizing Committee of the XVI. Diabetological Days with the

International Participation, Bratislava, Slovakia, 1.-3.6.2006.

RNDr. Martina Škopková, PhD.- Member of the Organizing Committee of XVI. Diabetological Days with the International

Participation, Bratislava, Slovakia, 1.-3.6.2006.

Mgr. Jozef Ukropec, PhD.- Member of the Organizing Committee of XVI. Diabetological Days with the International

Participation, Bratislava, Slovakia, 1.-3.6.2006.

Mgr. Barbara Ukropcová- Member of the Organizing Committee of XVI. Diabetological Days with the International

Participation, Bratislava, Slovakia, 1.-3.6.2006.

iii. List of employees who served as members of important international scientific

bodies (e.g. boards, committees, editorial boards of scientific journals)

2003:

Mgr. J. Benický, CSc.- Member of the European Peptide Society

Ing. J. Brtko, DrSc.- Corresponding Member of the European Thyroid Association (ETA) (elected

membership) - Member of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the International Editorial Board of the journal BIOMARKERS and

ENVIRONMENT (Czech Republic)

MUDr. R. Dunčko- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

RNDr. M. Ficková, CSc.- Member of the European Peptide Society

Mgr. D. Gašperíková, CSc.- Member of the European Association for the Study of Diabetes (EASD)

MUDr. R. Imrich, PhD.- Member of the European League Against Rheumatism

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Member of the Academia European (elected membership)- Vice-president of the Czech and Slovak Neurochemistry Society (elected membership)

(elected function)

45

- Member of the board of the Czech Neuropsychopharmacological Society (elected membership)

- Member of the Endocrine Society (USA) (elected membership) - Member of the “Societé de Neuroendocrinologie Expérimentale”, France (elected

membership) - Member of the “Societé de Physiologie”, France (elected membership) - Member of the European Society for Neurochemistry (elected membership) - Member of the European Peptide Society- Member of the International Study Group for Steroid Hormones- Member of the International Society for Gravitational Physiology- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY,

France, USA- Member of the International Editorial Board of the journal PEDIATRIC

ENDOCRINOLOGY, Poland

Ing. J. Jurčovičová, CSc.

- Member of the Board of the International Society for NeuroImmunomodulation- Member of the European Peptide Society- Member of the Czech Physiological Society

RNDr. A. Kiss, DrSc.- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- National Delegate for Slovak Republic of the European Federation of National Endocrine

Societies (EFES)- National Delegate for Slovak Republic of the International Endocrine Society (ISE) - Member of the International Diabetological Federation (IDF)- Member of the American Diabetological Society (ADA)- National Delegate for Slovak Republic of the COST B17 Management Committee- Associate Editor of the journal DIABETOLOGY (EU)- Member of the International Editorial Board of the journal ARCHIVES OF

PHYSIOLOGY AND BIOCHEMISTRY (The Netherlands)

Ing. J. Knopp, DrSc.- Corresponding Member of the European Thyroid Association (ETA) (elected

membership)

MUDr. J. Koška, PhD.- Member of the Growth Hormone Research Society- Member of the European Association for the Study of Diabetes (EASD)

MUDr. L. Kšinantová, PhD.- Member of the Growth Hormone Research Society

RNDr. R. Kvetňanský, DrSc.- Member of the Central European Academy of Science and Art (elected membership)

- Member of the Directorate of the World Stress Society (elected membership)

46

- Member of the Board of the International Society for Investigation of Stress (ISIS) (elected membership)

- Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Board of the International Society for Gravitational Physiology (elected

membership)- Member of the Board of the Czech and Slovak Neurochemistry (elected membership) - Member of the European Society for Neurochemistry- Member of the American Society for Neuroscience- Member of the European Society for Neuroscience- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal STRESS (USA, The

Netherlands)- Member of the International Editorial Board of the journal NEUROSCIENCE NEWS

(USA)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY

LETTERS (Sweden)

MUDr. P. Langer, DrSc.- Corresponding Member of the European Thyroid Association (ETA) (elected

membership) - Member of the International Society for Iodine Deficit Control (ICC/IDD)- Member of the International Editorial Board of the journal THE THYROID GLAND,

CLINICAL AND EXPERIMENTAL (Czech Republic)- Member of the International Editorial Board of the journal POLISH JOURNAL OF

ENDOCRINOLOGY (Poland)

MUDr. L. Macho, DrSc.- Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Academiae Scientiarum et Artium Europaea (elected membership) - Member of the Life Science Committee at IAA/IAF (elected membership) - Member of the Commission for Gravitation Physiology of IUPS (elected membership) - Foundation Member of the International Society for Gravitational Physiology- Foundation Member of the International Society for Developmental Neuroscience- Member of the European Society for Comparative Endocrinology- Member of the International Brain Research Organization- Member of the International Society for Pathophysiology- Member of the Scientific Commission COSPAR - Life Sciences - Member of the European Peptide Society- Honorary Member of the Czech Endocrine Society J.Ev.Purkyně- Member of the International Editorial Board of the journal INTERNATIONAL

JOURNAL GRAVITATION PHYSIOLOGY (USA)

MUDr. A. Makatsori- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

Mgr. M. Mlynárik- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

Mgr. Ľ. Szabová, PhD.- Member of the European Peptide Society

47

Ing. E. Šeböková, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- Member of the International Diabetological Federation (IDF)- Member of the American Diabetological Society (ADA)- National Delegate for Slovak Republic of the COST B17 Management Committee- National Delegate for Slovak Republic of the Programme Committee of the 6 th

Framework Programme, Priority 1, Life Sciences

MUDr. V. Štrbák, DrSc. - Member of the Endocrine Society (USA) (elected membership)- Member of the International Brain Research Organization (IBRO)- National Delegate for Slovak Republic of the International. Union of Physiological

Societies, IUPS Council member- National Delegate of the Federation of European Physiological Societies, FEPS Council

member - Member of the European Peptide Society- Editor for Europe of the journal CELLULAR AND MOLECULAR NEUROBIOLOGY

(USA)

MUDr. M. Vigaš, DrSc.- Member of the International Academy of Astronautics (IAA) (elected membership)- Member of the Czech and Slovak Neurochemistry Society

Ing. Š. Zorad, CSc.- National Delegate for Slovak Republic of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the European Association of Research Managers and Administrators

2004:

Mgr. J. Benický, CSc.- Member of the European Peptide Society- Member of the European Association for Study Diabetes (EASD)

Ing. J. Brtko, DrSc.- Corresponding Member of the European Thyroid Association (ETA) (elected

membership) - Member of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the International Editorial Board of the journal BIOMARKERS and

ENVIRONMENT (Czech Republic) - National Delegate of the Programme Committee of the 6th Framework Programme EC,

Priority 5, Food and Safety Food

MUDr. R. Dunčko- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

RNDr. M. Ficková, CSc.- Member of the European Peptide Society

Mgr. D. Gašperíková, CSc.

48

- Member of the European Association for the Study of Diabetes (EASD)

MUDr. R. Imrich, PhD.- Member of the European League Against Rheumatism

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Member of the Academia European (elected membership)- Vice-president of the Czech and Slovak Neurochemistry Society (elected membership)

(elected function)- Member of the board of the Czech Neuropsychopharmacological Society (elected

membership) - Member of the Endocrine Society (USA) (elected membership) - Member of the “Societé de Neuroendocrinologie Expérimentale”, France (elected

membership) - Member of the “Societé de Physiologie”, France (elected membership) - Member of the European Society for Neurochemistry (elected membership) - Member of the European Peptide Society- Member of the International Study Group for Steroid Hormones- Member of the International Society for Gravitational Physiology- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY,

France, USA- Member of the International Editorial Board of the journal PEDIATRIC

ENDOCRINOLOGY, Poland

Ing. J. Jurčovičová, CSc.- Member of the Board of the International Society for NeuroImmunomodulation- Member of the European Peptide Society- Member of the Czech Physiological Society

RNDr. A. Kiss, DrSc.- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- National Delegate for Slovak Republic of the European Federation of National Endocrine

Societies (EFES)- National Delegate for Slovak Republic of the International Endocrine Society (ISE) - Member of the International Diabetological Federation (IDF)- Member of the American Diabetological Society (ADA)- National Delegate for Slovak Republic of the COST B17 Management Committee- Member of the International Editorial Board of the journal ARCHIVES OF

PHYSIOLOGY AND BIOCHEMISTRY (The Netherlands)

Ing. J. Knopp, DrSc.- Corresponding Member of the European Thyroid Association (ETA) (elected

membership)

49

MUDr. J. Koška, PhD.- Member of the Growth Hormone Research Society- Member of the European Association for the Study of Diabetes (EASD)

MUDr. L. Kšinantová, PhD.- Member of the Growth Hormone Research Society

RNDr. R. Kvetňanský, DrSc.- Member of the Central European Academy of Science and Art (elected membership)

- Member of the Directorate of the World Stress Society (elected membership) - Member of the Board of the International Society for Investigation of Stress (ISIS)

(elected membership) - Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Board of the International Society for Gravitational Physiology (elected

membership)- Member of the Board of the Czech and Slovak Neurochemistry (elected membership) - Member of the European Society for Neurochemistry- Member of the American Society for Neuroscience- Member of the European Society for Neuroscience- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal STRESS (USA, The

Netherlands)- Member of the International Editorial Board of the journal NEUROSCIENCE NEWS

(USA)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY

LETTERS (Sweden)

MUDr. P. Langer, DrSc.- Corresponding Member of the European Thyroid Association (ETA) (elected

membership) - Member of the International Society for Iodine Deficit Control (ICC/IDD)- Member of the International Editorial Board of the journal THE THYROID GLAND,

CLINICAL AND EXPERIMENTAL (Czech Republic)- Member of the International Editorial Board of the journal POLISH JOURNAL OF

ENDOCRINOLOGY (Poland)

MUDr. L. Macho, DrSc.- Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Academiae Scientiarum et Artium Europaea (elected membership) - Member of the Life Science Committee at IAA/IAF (elected membership) - Member of the Commission for Gravitation Physiology of IUPS (elected membership) - Foundation Member of the International Society for Gravitational Physiology- Foundation Member of the International Society for Developmental Neuroscience- Member of the European Society for Comparative Endocrinology- Member of the International Brain Research Organization- Member of the International Society for Pathophysiology- Member of the Scientific Commission COSPAR - Life Sciences - Member of the European Peptide Society- Honorary Member of the Czech Endocrine Society J.Ev.Purkyně- Member of the International Editorial Board of the journal INTERNATIONAL

JOURNAL GRAVITATION PHYSIOLOGY (USA)

MUDr. A. Makatsori

50

- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

Mgr. M. Mlynárik- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

MUDr. A. Penesová- Member of the European Association for Study Diabetes (EASD)

Mgr. Z. Pirník- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

MUDr. Ž. Rádiková, PhD.- Member of the European Association for Study Diabetes (EASD)

Mgr. Ľ. Sabová, PhD.- Member of the European Peptide Society

Ing. E. Šeböková, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- Member of the International Diabetological Federation (IDF)- Member of the American Diabetological Society (ADA)- National Delegate for Slovak Republic of the COST B17 Management Committee- National Delegate for Slovak Republic of the Programme Committee of the 6 th

Framework Programme, Priority 1, Life Sciences

MUDr. V. Štrbák, DrSc. - Member of the Endocrine Society (USA) (elected membership)- Member of the International Brain Research Organization (IBRO)- National Delegate for Slovak Republic of the International Union of Physiological

Societies, IUPS Council member- National Delegate of the Federation of European Physiological Societies, FEPS Council

member - Member of the European Peptide Society- Editor for Europe of the journal CELLULAR AND MOLECULAR NEUROBIOLOGY

(USA)- Member of the Society for Neuroscience- Member of the American Diabetes Association- National Delegate of the Programme Committee of the 6th Framework Programme EC,

Priority 1, Life Sciences

MUDr. M. Vigaš, DrSc.- Member of the International Academy of Astronautics (IAA) (elected membership)- Member of the Czech and Slovak Neurochemistry Society

Ing. Š. Zorad, CSc.- National Delegate for Slovak Republic of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the European Association of Research Managers and Administrators

51

2005:

Mgr. J. Bakoš- Member of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society

Mgr. J. Benický, CSc.- Member of the European Peptide Society- Member of the European Association for Study Diabetes (EASD)

Ing. J. Brtko, DrSc.- Member of the European Thyroid Association (ETA) (elected membership) - Member of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the International Editorial Board of the journal BIOMARKERS and

ENVIRONMENT (Czech Republic) - National Delegate (expert) of the Programme Committee of the 6 th Framework

Programme EC, Priority 5, Food and Safety Food

MUDr. R. Dunčko- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

RNDr. M. Ficková, CSc.- Member of the European Peptide Society

Mgr. D. Gašperíková, CSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the American Association for Diabetes (ADA)- Member of the International Federation for diabetes (IDF)

MUDr. R. Imrich, PhD.- Member of the European League Against Rheumatism (EULAR)- Member of the International Society of Psychoneuroendocrinology (ISPNE)

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Member of the Academia European (elected membership)- Vice-president of the Czech and Slovak Neurochemistry Society (elected membership)

(elected function)- Member of the board of the Czech Neuropsychopharmacological Society (elected

membership) - Member of the Endocrine Society (USA) (elected membership) - Member of the “Societé de Neuroendocrinologie Expérimentale”, France (elected

membership) - Member of the “Societé de Physiologie”, France (elected membership) - Member of the European Society for Neurochemistry (elected membership) - Member of the European Peptide Society- Member of the International Study Group for Steroid Hormones- Member of the International Society for Gravitational Physiology- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY,

France, USA

52

- Member of the International Editorial Board of the journal PEDIATRIC ENDOCRINOLOGY, Poland

- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY LETTERS, Sweden

Ing. J. Jurčovičová, CSc.

- Member of the Board of the International Society for NeuroImmunomodulation- Member of the European Peptide Society- Member of the Czech Physiological Society

RNDr. A. Kiss, DrSc.- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

Prof. MUDr. I. Klimeš, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- National Delegate for Slovak Republic of the European Federation of National Endocrine

Societies (EFES)- National Delegate for Slovak Republic of the International Endocrine Society (ISE) - Member of the International Diabetological Federation (IDF)- Member of the American Diabetological Society (ADA)- National Delegate for Slovak Republic of the COST B17 Management Committee- Member of the International Editorial Board of the journal ARCHIVES OF

PHYSIOLOGY AND BIOCHEMISTRY (The Netherlands)

MUDr. J. Koška, PhD.- Member of the Growth Hormone Research Society- Member of the European Association for the Study of Diabetes (EASD)

RNDr. R. Kvetňanský, DrSc.- Member of the Central European Academy of Science and Art (elected membership) - Member of the Directorate of the World Stress Society (elected membership) - Member of the Board of the International Society for Investigation of Stress (ISIS)

(elected membership) - Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Board of the International Society for Gravitational Physiology (elected

membership)- Member of the Board of the Czech and Slovak Neurochemistry (elected membership) - Member of the European Society for Neurochemistry- Member of the American Society for Neuroscience- Member of the European Society for Neuroscience- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal STRESS (USA, The

Netherlands)- Member of the International Editorial Board of the journal NEUROSCIENCE NEWS

(USA)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY

LETTERS (Sweden)

MUDr. P. Langer, DrSc.

53

- Corresponding Member of the European Thyroid Association (ETA) (elected membership)

- Member of the International Society for Iodine Deficit Control (ICC/IDD)- Member of the International Editorial Board of the journal THE THYROID GLAND,

CLINICAL AND EXPERIMENTAL (Czech Republic)- Member of the International Editorial Board of the journal POLISH JOURNAL OF

ENDOCRINOLOGY (Poland)- Member of the International Editorial Board of the journal ENDOKRYNOLOGIA

POLSKA, Poland

MUDr. L. Macho, DrSc.- Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Academiae Scientiarum et Artium Europaea (elected membership) - Member of the Life Science Committee at IAA/IAF (elected membership) - Member of the Commission for Gravitation Physiology of IUPS (elected membership) - Foundation Member of the International Society for Gravitational Physiology- Foundation Member of the International Society for Developmental Neuroscience- Member of the European Society for Comparative Endocrinology- Member of the International Brain Research Organization- Member of the International Society for Pathophysiology- Member of the Scientific Commission COSPAR - Life Sciences - Member of the European Peptide Society- Honorary Member of the Czech Endocrine Society J.Ev.Purkyně- Member of the International Editorial Board of the journal INTERNATIONAL

JOURNAL GRAVITATION PHYSIOLOGY (USA)

Mgr. M. Mlynárik- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

MUDr. A. Penesová- Member of the European Association for Study Diabetes (EASD)

Mgr. Z. Pirník- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

MUDr. Ž. Rádiková, PhD.- Member of the European Association for Study Diabetes (EASD)

Mgr. Ľ. Sabová, PhD.- Member of the European Peptide Society

Ing. E. Šeböková, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- Member of the International Diabetological Federation (IDF)- Member of the American Diabetological Society (ADA)

RNDr. M. Škopková, PhD.- Member of the European Association for the Study of Diabetes (EASD)

54

MUDr. V. Štrbák, DrSc. - Member of the Endocrine Society (USA) (elected membership)- Member of the International Brain Research Organization (IBRO)- National Delegate for Slovak Republic of the International Union of Physiological

Societies, IUPS Council member - National Delegate of the Federation of European Physiological Societies, FEPS Council

member - Member of the European Peptide Society- Editor for Europe of the journal CELLULAR AND MOLECULAR NEUROBIOLOGY

(USA)- Member of the Society for Neuroscience- Member of the American Diabetes Association- National Delegate of the Programme Committee of the 6th Framework Programme EC,

Priority 1, Life Sciences- Member of the International Advisory Board of the journal PHYSIOLOGICAL

RESEARCH, Czech Republic- Member of the International Advisory Board of the journal IUGOSLAVICA

PHYSIOLOGICA ET PHARMACOLOGICA ACTA, Serbia

MUDr. M. Vigaš, DrSc.- Member of the International Academy of Astronautics (IAA) (elected membership)- Member of the Czech and Slovak Neurochemistry Society

Ing. Š. Zorad, CSc.- National Delegate for Slovak Republic of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the European Association of Research Managers and Administrators

2006:

Mgr. J. Bakoš- Member of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the Czech Neuropsychopharmacological Society (elected membership)

Mgr. J. Benický, CSc.- Member of the European Peptide Society- Member of the European Association for Study Diabetes (EASD)

Ing. J. Brtko, DrSc.- Member of the European Thyroid Association (ETA) (elected membership) - Member of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the International Editorial Board of the journal BIOMARKERS and

ENVIRONMENT (Czech Republic) - National Delegate (expert) of the Programme Committee of the 6 th Framework

Programme EC, Priority 5, Food and Safety Food

MUDr. R. Dunčko- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

RNDr. M. Ficková, CSc.

55

- Member of the European Peptide Society

Mgr. D. Gašperíková, CSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the American Association for Diabetes (ADA)- Member of the International Federation for diabetes (IDF)

Mgr. Nataša Hlaváčová- Member of the Czech Neuropsychopharmacological Society (elected membership)

MUDr. R. Imrich, PhD.- Member of the European League Against Rheumatism (EULAR)- Member of the International Society of Psychoneuroendocrinology (ISPNE)

Prof. PharmDr. D. Ježová, DrSc.- Member of the Academia European (elected membership)- Vice-president of the Czech and Slovak Neurochemistry Society (elected membership)

(elected function)- Member of the board of the Czech Neuropsychopharmacological Society (elected

membership) - Member of the Endocrine Society (USA) (elected membership) - Member of the “Societé de Neuroendocrinologie Expérimentale”, France (elected

membership) - Member of the “Societé de Physiologie”, France (elected membership) - Member of the European Society for Neurochemistry (elected membership) - Member of the European Peptide Society- Member of the International Study Group for Steroid Hormones- Member of the International Society for Gravitational Physiology- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY,

France, USA- Member of the International Editorial Board of the journal PEDIATRIC

ENDOCRINOLOGY, Poland- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY

LETTERS, Sweden

Ing. J. Jurčovičová, CSc.

- Member of the Board of the International Society for NeuroImmunomodulation- Member of the European Peptide Society- Member of the Czech Physiological Society

RNDr. A. Kiss, DrSc.- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

Prof. MUDr. I. Klimeš, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- National Delegate for Slovak Republic of the European Federation of National Endocrine

Societies (EFES)- National Delegate for Slovak Republic of the International Endocrine Society (ISE) - Member of the International Diabetological Federation (IDF)

56

- Member of the American Diabetological Society (ADA)- National Delegate for Slovak Republic of the COST B17 Management Committee- Member of the International Editorial Board of the journal ARCHIVES OF

PHYSIOLOGY AND BIOCHEMISTRY (The Netherlands)

MUDr. J. Koška, PhD.- Member of the Growth Hormone Research Society- Member of the European Association for the Study of Diabetes (EASD)

RNDr. R. Kvetňanský, DrSc.- Member of the Central European Academy of Science and Art (elected membership) - Member of the Directorate of the World Stress Society (elected membership) - Member of the Board of the International Society for Investigation of Stress (ISIS)

(elected membership) - Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Board of the International Society for Gravitational Physiology (elected

membership)- Member of the Board of the Czech and Slovak Neurochemistry (elected membership) - Member of the European Society for Neurochemistry- Member of the American Society for Neuroscience- Member of the European Society for Neuroscience- Member of the International Brain Research Organization (IBRO)- Member of the International Editorial Board of the journal STRESS (USA, The

Netherlands)- Member of the International Editorial Board of the journal NEUROSCIENCE NEWS

(USA)- Member of the International Editorial Board of the journal NEUROENDOCRINOLOGY

LETTERS (Sweden)

MUDr. P. Langer, DrSc.- Corresponding Member of the European Thyroid Association (ETA) (elected

membership) - Member of the International Society for Iodine Deficit Control (ICC/IDD)- Member of the International Editorial Board of the journal THE THYROID GLAND,

CLINICAL AND EXPERIMENTAL (Czech Republic)- Member of the International Editorial Board of the journal POLISH JOURNAL OF

ENDOCRINOLOGY (Poland)- Member of the International Editorial Board of the journal ENDOKRYNOLOGIA

POLSKA, Poland

MUDr. L. Macho, DrSc.- Member of the International Academy of Astronautics (IAA) (elected membership) - Member of the Academiae Scientiarum et Artium Europaea (elected membership) - Member of the Life Science Committee at IAA/IAF (elected membership) - Member of the Commission for Gravitation Physiology of IUPS (elected membership) - Foundation Member of the International Society for Gravitational Physiology- Foundation Member of the International Society for Developmental Neuroscience- Member of the European Society for Comparative Endocrinology- Member of the International Brain Research Organization- Member of the International Society for Pathophysiology- Member of the Scientific Commission COSPAR - Life Sciences - Member of the European Peptide Society- Honorary Member of the Czech Endocrine Society J.Ev.Purkyně

57

- Member of the International Editorial Board of the journal INTERNATIONAL JOURNAL GRAVITATION PHYSIOLOGY (USA)

Mgr. M. Mlynárik- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

MUDr. B. Mravec, PhD.- Member of the Czech Neuropsychopharmacological Society (elected membership)

MUDr. A. Penesová- Member of the European Association for Study Diabetes (EASD)

Mgr. Z. Pirník- Member of the Czech Neuropsychopharmacological Society (elected membership) - Member of the Czech and Slovak Neurochemistry Society

MUDr. Ž. Rádiková, PhD.- Member of the European Association for Study Diabetes (EASD)

Mgr. Ľ. Sabová, PhD.- Member of the European Peptide Society

Ing. E. Šeböková, DrSc.- Member of the European Association for the Study of Diabetes (EASD)- Member of the Federation of the Danube Diabetes Mellitus Symposia (FID), member of

the International Organizing Committee (elected membership)- Member of the International Diabetological Federation (IDF)- Member of the American Diabetological Society (ADA)RNDr. M. Škopková, PhD.- Member of the European Association for the Study of Diabetes (EASD)

MUDr. V. Štrbák, DrSc. - Member of the Endocrine Society (USA) (elected membership)- Member of the International Brain Research Organization (IBRO)- National Delegate for Slovak Republic of the International Union of Physiological

Societies, IUPS Council member- National Delegate of the Federation of European Physiological Societies, FEPS Council

member- Member of the International Society for Pathophysiology, ISP Council member - Member of the European Peptide Society- Editor for Europe of the journal CELLULAR AND MOLECULAR NEUROBIOLOGY

(USA)- Member of the Society for Neuroscience- Member of the American Diabetes Association- National Delegate of the Programme Committee of the 6th Framework Programme EC,

Priority 1, Life Sciences- Member of the International Advisory Board of the journal PHYSIOLOGICAL

RESEARCH, Czech Republic- Member of the International Advisory Board of the journal IUGOSLAVICA

PHYSIOLOGICA ET PHARMACOLOGICA ACTA, Serbia

MUDr. M. Vigaš, DrSc.

58

- Member of the International Academy of Astronautics (IAA) (elected membership)- Member of the Czech and Slovak Neurochemistry Society

Ing. Š. Zorad, CSc.- National Delegate for Slovak Republic of the European Peptide Society- Member of the Czech and Slovak Neurochemistry Society- Member of the European Association of Research Managers and Administrators

iv. List of international scientific awards and distinctions

2003:Mgr. J. Benický, PhD.- Awarded by the travel COST grant

MUDr. R. Dunčko- Award of the Czech Neuropsychopharmacological Society for the Best Paper (Ježová D.,

Dunčko R.: Enhancement of stress-induced pituitary hormone release and cardiovascular ac-tivation by antidepressant treatment in healthy men. J Psychopharm. 16: 235-240, 2002)

- Achievement of the grant of the Czech Neuropsychopharmacological Society supporting presentation of the data in International Conferences

Mgr. D. Gašperíková, CSc.- Awarded by of the Shorm Term Scientific Mission COST grant for 14 days stay at the

Leiden University Medical Center, Leiden, Netherlands

MUDr. R. Imrich, PhD.- Awarded by the EULAR travel grant for participation at the European League Against

Rheumatism Congress in Lisboa, Portugal, 16.-23.6.2003

- Awarded by the EULAR grant enabling three month study stay at the Laboratory of Neuroendocrinoimmunology in the Free University of Brussels, Bruxelles, Belgium

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Award of the Czech Neuropsychopharmacological Society for the Best Paper (Ježová D.,

Dunčko R.: Enhancement of stress-induced pituitary hormone release and cardiovascular ac-tivation by antidepressant treatment in healthy men. J Psychopharm. 16: 235-240, 2002)

MUDr. A. Makatsori- Awarded by the grant of the Czech Neuropsychopharmacological Society supporting

presentation of the data in International Conferences

Mgr. M. Mlynárik- Awarded by the IBRO grant supporting attendance at the 11th International Symposium:

New frontiers of neurochemistry and neurophysics on diagnosis and treatment of neurological diseases, Florence, Italy

RNDr. M. Najvirtová- Awarded by the Travel Award The Welcome Trust, UK

Mgr. Z. Pirník

59

- Achievement of the ISN grant supporting attendance at the 11 th International Symposium: New frontiers of neurochemistry and neurophysics on diagnosis and treatment of neurological diseases, Florence, Italy

MUDr. V. Štrbák, DrSc.- Laufberger Plaque Award of the Czech Physiological Society LSJEP

2004:

Mgr. Z. Bačová- Awarded by the travel IBRO grant for attendance of the Summer School in Crimea,

Ukraine

MUDr. R. Imrich, PhD.- Awarded by travel grant for participation at the Annual Congress of Rheumatology,

Berlin, Germany, 9.-12. 06. 2004.- Awarded by the EULAR grant enabling three month study stay at the Laboratory of

Neuroendocrinoimmunology in the Free University of Brussels, Bruxelles, Belgium

2005:

RNDr. Ján Bakoš- Awarded by the grant IBRO for participation at the 5 th International symposium on

experimental and clinical neurobiology, Stará Lesná, Slovakia, 19.-22.9. 2005

Mgr. D. Gašperíková, CSc.- Awarded by an EASD Stayment Grant for participation in the European Diabetes

Congress, Athens, Greece, 12.-15.9. 2005

Mgr. Martin Mlynárik- Awarded by the grant ČNPS for participation at the 8 th World Congress of Biological

Psychiatry, Austria Center Vienna, Vienna, Austria, 28.6 – 3.7. 2005

RNDr. M. Škopková, PhD - Awarded by the grant COST B17 for one month study stay at the German Diabetes Center

Institute of Clinical Biochemistry and Pathobiochemistry, Dusseldorf, Germany

2006:

RNDr. Ján Bakoš- Awarded by the Literary Fund support for young scientists for participation at the Joint

Meeting of The German Society of Physiology and The Federation of European Physiological Societies, Munich, Germany, 26-29.3.2006.

- Awarded by the IBRO grant for participation at the 11th Meeting of the Czech and Slovak Neurochemical Society, Martin, Slovakia, 6.-10.9.2006.

Mgr. Daniela Gašperíková, CSc.- Awarded by the European Association for Study Diabetes grant for participation at the

IEASD Annual Meeting, Copenhagen – Malmoe, Denmark – Sweden, 14.-17.9.2006. - Awarded by the grant of the Slovak Diabetological Society for participation at the 66th

ADA Scientific Sessions, Washington DC“, USA 9.–13.6.2006.

Prof. PharmDr. Daniela Ježová, DrSc.

60

- Award of the Czech Neuropsychopharmacological Society for the Best Paper of the Year.- Award of the Czech Society for Experimental and Clinical Pharmacology and Toxicology

for the Best Paper of the Year.

RNDr. Richard Kvetňanský, DrSc.- Prolonged function of the „Visiting Professor“ in the Center of Alcohol Studies, Rutgers

University, Piscataway N.J. USA , since 1.7.2006

Mgr. Jozef Ukropec, PhD.Awarded by the grant of the German Diabetes Centre for 14 days study stay at the Institute of Clinical Biochemistry and Pathobiochemistry, Düsseldorf, Germany.

National position of the individual researchers

i. List of invited/keynote presentations at national conferences documented by

an invitation letter or programme

None

ii. List of employees who served as members of organising and programme

committees of national conferences

Prof. MUDr. Iwar Klimeš, DrSc.- member of the Program Committee of all four national Obesity Days in Nimnica

(2003, 2004, 2005, 2006)

iii. List of employees serving in important national scientific bodies (e.g. boards,

committees, editorial boards of scientific journals)

A/ Participation in Editorial Board of national journals

1/ Chief Editors of national journals

RNDr. R. Kvetňanský, DrSc., Chief Ed. ENDOCRINE REGULATIONS (2003, 2004, 2005, 2006)2/ Members of Editorial Board of ENDOCRINE REGULATIONS

Ing. J. Brtko, DrSc. (2003, 2004, 2005, 2006)MUDr. R. Imrich, PhD. (2003, 2004)Prof. PharmDr. D. Ježová, DrSc. (2003, 2004, 2005, 2006)Prof. MUDr. I. Klimeš, DrSc. (2003, 2004, 2005, 2006)MUDr. P. Langer, DrSc. (2003, 2004, 2005, 2006)MUDr. L. Macho, DrSc. (2003, 2004, 2005, 2006)MUDr. Ž. Rádiková, PhD. (2003, 2004)MUDr. V. Štrbák, DrSc. (2003, 2004, 2005, 2006)

3/ Members of Editorial Board of BRATISLAVSKE LEKARSKE LISTY

Prof. MUDr. I. Klimeš, DrSc. (2003, 2004, 2005, 2006)

61

4/ Members of Editorial Board of LABORATORY DIAGNOSIS

Ing. E. Šeböková, DrSc. (2003, 2004)

5/ Members of Editorial Board of GENERAL PHYSIOLOGY AND BIOPHYSICS

MUDr. V. Štrbák, DrSc. (2003, 2004, 2005, 2006) - EditorIng. J. Brtko, DrSc. (2004, 2005, 2006)

6/ Members of Editorial Board of BIOLOGIA

RNDr. A. Kiss, DrSc., (2006)

7/ Members of Editorial Board of DIABETES AND OBESITY

Prof. MUDr. I. Klimeš, DrSc., (2006)

8/ Members of Editorial Board of SAS NEWS

Ing. J. Brtko, DrSc., (2004, 2005, 2006)

B/ Participation in National Scientific Societies

2003

Assoc. Prof. D. Ježová, DrSc.- Slovak Physiological Society (board member)- Slovak Literary Fund (chairman of jury for Medial and Biological Section)

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Slovak Endocrine Society (president)- Slovak Diabetes Society (board member)- Slovak Diabetes Society-Grant Agency (president)- Slovak Diabetes Society-Obesity Section (board member)- Slovak Diabetes Society-Lipid Section (board member)

Ing. J. Knopp, DrSc.- Slovak Biochemical and Molecular Biology Society (president)- Executive Committee of Slovak Scientific Board for Slovak Research Committee

Societies (president)

MUDr. P. Langer, DrSc.- Committee of Slovak Endocrine Society-Iodine Subcommittee (president)- Slovak Committee for UNICEF (participator in iodine prophylaxis)

MUDr. L. Macho, DrSc.- Slovak Physiological Society (honorary board member)

62

Ing. E. Šeböková, DrSc.- Slovak Diabetes Society- Lipid Section (board member) - Committee of Slovak Endocrine Society- Iodine subcommittee (member)

MUDr. V. Štrbák, DrSc.- Slovak Physiological Society (president)

2004

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Slovak Physiological Society (board member)- Slovak Literary Fund (chairman of jury for Medial and Biological Section)

RNDr. A. Kiss, DrSc.- Ethic Committee (Institute of molecular physiology and genetic, president)

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Slovak Endocrinological Society (president)- Slovak Diabetes Society (board member)- Slovak Diabetes Society-Grant Agency (president)- Slovak Diabetes Society-Obesity Section (board member)- Slovak Diabetes Society-Lipid Section (board member)

MUDr. P. Langer, DrSc.- Committee of Slovak Endocrine Society-Iodine subcommittee (president)- Slovak Committee for UNICEF (participator in iodine prophylaxis)

MUDr. L. Macho, DrSc.- Slovak Physiological Society (honorary board member)

Ing. E. Šeböková, DrSc.- Slovak Diabetes Society-Lipid Section (board member)- Committee of Slovak Endocrinological Society-Iodine subcommittee (member)

MUDr. V. Štrbák, DrSc.- Slovak Physiological Society (president)

2005

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Slovak Physiological Society (board member)- Slovak Literary Fund (chief of jury for Medial and Biological Section)- SAS Learned Society (member)

Prof. MUDr. I. Klimeš, DrSc.- Slovak Endocrinological Society (president)- Slovak Diabetes Society (board member)- Slovak Diabetes Society-Grant Agency (president)- Slovak Diabetes Society-ObesitySection (board member)- Slovak Diabetes Society-Lipid Section (board member)- SAS Learned Society (board member)

63

RNDr. R. Kvetňanský, DrSc.- Slovak Neuroscience Society of SAS (scientific secretary)- SAS Learned Society (member)

MUDr. P. Langer, DrSc.- Committee of Slovak Endocrine Society-Iodine Subcommittee (president)- Slovak Committee for UNICEF (participator in iodine prophylaxis)- SAS Learned Society (emeritus member)

MUDr. L. Macho, DrSc.- Slovak Physiological Society (honorary board member)- Slovak Endocrine Society (honorary member)- SAS Learned Society (emeritus member)

Ing. E. Šeböková, DrSc.- SAS Learned Society (member)

MUDr. V. Štrbák, DrSc.- Slovak Physiological Society (president)

MUDr. M. Vigaš, DrSc.- SAS Learned Society (emeritus member)

2006

Prof. PharmDr. D. Ježová, DrSc.- Slovak Physiological Society (board member)- Slovak Literary Fund (chairman of jury for Medial and Biological Section)- SAS Learned Society (member)

Prof. MUDr. I. Klimeš, DrSc.- Slovak Endocrine Society (president)- Slovak Endocrine Society (honorary member)- Slovak Diabetes Society (board member)- Slovak Diabetes Society-Grant Agency (president)- Slovak Diabetes Society-Obesity Section (board member)- Slovak Diabetes Society-Lipid Section (board member)- SAS Learned Society (board member)

RNDr. R. Kvetňanský, DrSc.- Slovak Neuroscience Society of SAS (board member)- SAS Learned Society (member)

MUDr. P. Langer, DrSc.- Committee of Slovak Endocrine Society-Iodine Subcommittee (president)- Slovak Committee for UNICEF (participator in iodine prophylaxis)- SAS Learned Society (emeritus member)

MUDr. L. Macho, DrSc.- Slovak Physiological Society (honorary board member)- Slovak Endocrine Society (honorary member)- SAS Learned Society (emeritus member)

64

MUDr. M. Vigaš, DrSc.- SAS Learned Society (emeritus member)

MUDr. V. Štrbák, DrSc.- Slovak Physiological Society (president)

C/ Memberships in Slovak Academy of Sciences Committees

2003

Ing. J. Brtko, DrSc.- VEGA Grant Committee, Section 8 (member)- Intellectual Demesne Committee (member)

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Scientific Collegium of SAS for Medical Science (scientific secretary)- Research Qualification Appraising Committee (member)- Accreditation Committee (member)- Accreditation Committee-Medical Institutes Subcommittee (president)

RNDr. A. Kiss, DrSc.- Bioethics Committee (secretary)

Ing. J. Knopp, DrSc.- Member of the SAS Chairmen Board- Chairmen Board-the II. Scientific Department (deputy president)- Committee for Foreign Contacts (member)- Committee for Economic Issues (member)- MVTS (member)- Editorial Board (member)- Pro Sciencia Foundation (chief)

RNDr. R. Kvetňanský, DrSc.- Scientific Collegium of SAS for Molecular and Cell Biology (member)

MUDr. L. Macho, DrSc.- VEGA Grant Committee (board member) - VEGA Grant Committee, Section 7 (deputy president)

Ing. E. Šeböková, DrSc.- VEGA Grant Committee, Section 9 (member)

MUDr. V. Štrbák, DrSc.- Scientific Collegium of SAS for Medical Science (deputy president) - Research Qualification Appraising Committee (member)- Scientific Education Committee (member)- Editorial Committee (member)- Ethical Committee (member)- VEGA Grant Committee, Section 7 (member)

2004

65

Ing. J. Brtko, DrSc.- VEGA Grant Committee, Section 8 (member)- Intellectual Demesne Committee (member)

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Scientific Collegium of SAS (scientific secretary)- Research Qualification Appraising Committee (member)- Accreditation Committee (member)- Accreditation Committee-Medical Institutes Subcommittee (president)

RNDr. A. Kiss, DrSc.- Bioethics Committee (secretary)

Assoc. Prof. MUDr. Iwar Klimeš, DrSc.- Scientific board of the UMFG Institute (member)

Ing. J. Knopp, DrSc.- Member of the SAS Chairmen Board- Chairmen Board-the II. Scientific Department (deputy president)- Committee for Foreign Contacts (member)- Committee for Economic Issues (member)- MVTS (member)- Editorial Board (member)- Pro Sciencia Foundation (president)

RNDr. R. Kvetňanský, DrSc.- Scientific Collegium of SAS for Molecular and Cell Biology (member)

MUDr. L. Macho, DrSc.- VEGA Grant Committee (board member) - VEGA Grant Committee, Section 7 (deputy president)

Ing. E. Šeböková, DrSc.- VEGA Grant Committee, Section 9 (member)

MUDr. V. Štrbák, DrSc.- Scientific Collegium of SAS (Medical Science, deputy president) - Research Qualification Appraising Committee (member)- Scientific Education Committee (member)- Editorial Committee (member)- VEGA Grant Committee, Section 7 (member)

2005

Ing. J. Brtko, DrSc.- VEGA Grant Committee, Section 8 (member)- Intellectual Demesne Committee (member)

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Scientific Collegium of SAS (scientific secretary)- Research Qualification Appraising Committee (member)- Accreditation Committee (member)

66

- Accreditation Committee-Medical Institutes Subcommittee (president)

RNDr. A. Kiss, DrSc.- SAS Parliament (board member)- Chairmen Board-the II. Scientific Department (member)- Committee for Foreign Contacts (member)- Centre of Excellence Counsel Committee (member)- VEGA Grant Committee, Section 7 (member)

Prof. MUDr. Iwar Klimeš, DrSc.- Economic Committee (member)- Scientific board of the UMFG Institute (member)

Ing. J. Knopp, DrSc.- Member of the SAS Chairmen Board- Chairmen Board-the II. Scientific Department (deputy president)- Committee for Foreign Contacts (member)- Committee for Economic Issues (member)- MVTS (member)- Editorial Board (member)- Pro Sciencia Foundation (president)

RNDr. R. Kvetňanský, DrSc.- Scientific Collegium of SAS for Molecular and Cell Biology (member)

MUDr. L. Macho, DrSc.- VEGA Grant Committee (board member) - VEGA Grant Committee, Section 7 (deputy president)

MUDr. V. Štrbák, DrSc.- Scientific Collegium of SAS (Medical Science, deputy president) - Research Qualification Appraising Committee (member)- Scientific Education Committee (member)- Editorial Committee (member)- Ethical Committee (member)- VEGA Grant Committee, Section 7 (member)

2006

Ing. J. Brtko, DrSc.- VEGA Grant Committee, Section 8 (member)

Prof. D. Ježová, DrSc.- Scientific Collegium of SAS-Medical Science (scientific secretary)- Evaluation Committee of the II. SAS Scientific Department (member)- Research Qualification Appraising Committee (member)- Accreditation Committee of SAS (member)

RNDr. A. Kiss, DrSc.- SAS Parliament Board (member)- Chairmen Board (II. Scientific Department, member)- Committee for Foreign contacts (member)- Centre of Excellence Counsel Committee (member)

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- VEGA Grant Committee, Section 7 (member)

Prof. MUDr. Iwar Klimeš, DrSc.- Economic Committee (member)- Scientific Board of the UMFG Institute (member)

RNDr. R. Kvetňanský, DrSc.- Scientific Collegium of SAS for Molecular and Cell Biology (member)

MUDr. L. Macho, DrSc.- Accreditation Committee of the SAS II. Scientific Department (member)

MUDr. V. Štrbák, DrSc.- Scientific Collegium of SAS -Medical Science (deputy president) - Editorial Committee (member)- Ethical Committee (member)- Scientific Board of the UVS Institute (member)

D/ Membership and Activities in SR Government Committees

2003

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Slovak Literary Fund (Scientific and Computer Section, board member)

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Slovak Scientific Degree Granting Committee (SR Education Ministry, chairman)

Ing. J. Knopp, DrSc.- Cardiogenomica SPVV subprogramm (deputy president)

RNDr. R. Kvetňanský, DrSc.- Operating Group No. 23-Ministry of Economy SR (member)- Slovak Commission for Research and Peaceful Use of Space at the Council for Science

and Technology of the Government of the SR (president)

RNDr. R. Kvetňanský, DrSc. a MUDr. L. Macho, DrSc.- Report of Cosmos Activities in SR (participated in its elaboration for SR mission in

OSN– COPUOS Committee)- Concept of State Policy for Slovak Commission for Research and Peaceful Use of Space

at the Council for Science and Technology of the Government of the SR

MUDr. P. Langer, DrSc.- Iodine Committee of SR Health Ministry (member)

MUDr. L. Macho, DrSc.- Slovak Commission for Research and Peaceful Use of Space at the Council for Science

and Technology of the Government of the SR (scientific secretary) - Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Normal and

Pathological Physiology of the Slovak Republic

68

Ing. E. Šeböková, DrSc.- Programm Committee for 6. FP ES „Integrating and Strengthening the European

Research Area“ (delegate- appointed by SR Health Ministry)

MUDr. V. Štrbák, DrSc.- Research and Technic Supporting Counsel Agency (APVT, member)- Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Animal Physiology and Etology of the Slovak Republic

2004

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Slovak Literary Fund-Scientific and Computer Section (board member)

Assoc. Prof. MUDr. I. Klimeš, DrSc.- Slovak Scientific Degree Granting Committee (SR Education Ministry, chairman)

Ing. J. Knopp, DrSc.- Cardiogenomica SPVV subprogramm (deputy president)

RNDr. R. Kvetňanský, DrSc.- Operating Group No. 23 (Ministry of Economy SR, member)- Slovak Commission for Research and Peaceful Use of Space at the Council for Science

and Technology of the Government of the SR (president)- High Level Space Policy Group (European Committee, delegate)- 1st Space Council for European Committee, delegate)

RNDr. R. Kvetňanský, DrSc. a MUDr. L. Macho, DrSc.- Report of Cosmos Activities in SR (participated in the elaboration for SR mission in OSN– COPUOS Committee)- Concept of State Policy for Slovak Commission for Research and Peaceful Use of Space

at the Council for Science and Technology of the Government of the SR - Questionnaire EC of Space Council for SR standpoint (participated in the elaboration)

MUDr. P. Langer, DrSc.- Iodine Committee of SR Health Ministry (member)

MUDr. L. Macho, DrSc.- Slovak Commission for Research and Peaceful Use of Space at the Council for Science

and Technology of the Government of the SR (member)- Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Normal and

Pathological Physiology of the Slovak Republic

Ing. E. Šeböková, DrSc.- Program Committee for 6. FP ES „Integrating and Strengthening the European

Research Area“ (delegate appointed by SR Health Ministry)

MUDr. V. Štrbák, DrSc. - SR Program Committee of the 6th Framework Program of ES, priority No.1 - Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Animal

Physiology and Etology of the Slovak Republic

69

2005

Ing. J. Brtko, DrSc.- Program Board of 6 FP ES „Integrating and Strengthening the European Research Area“ priority 5 (appointed as independent expert by SR Education Ministry)

Assoc. Prof. PharmDr. D. Ježová, DrSc.- Slovak Literary Fund-Scientific and Computer Section (board member)

Prof. MUDr. I. Klimeš, DrSc.- Slovak Scientific Degree Granting Committee (SR Education Ministry, chairman)

Ing. J. Knopp, DrSc.Cardiogenomica SPVV subprogramm (deputy president)

RNDr. R. Kvetňanský, DrSc.- Operating Group No. 23 (Ministry of Economy SR, member)- Cosmos Research and Peace Realization Committee (SR Counsel Government,

president)- High Level Space Policy Group (European Committee, delegate)- 2nd and 3rd Space Council for European Committee, delegate) RNDr. R. Kvetňanský, DrSc. a MUDr. L. Macho, DrSc.- Report of Cosmos Activities in SR (participated in the elaboration for SR mission in OSN– COPUOS Committee)- Concept of State Policy for Cosmos Research and Peace Realization Committee (SR

Counsel Government, participated in the elaboration) - Questionnaire EC of Space Council for SR standpoint (participated in the elaboration)

RNDr. A. Kiss, DrSc.- Board member of the committee for Doctor of Sciences (DSc.) habilitation in Animal

Physiology and Etology of the Slovak Republic

MUDr. P. Langer, DrSc.- Iodine Committee of SR Health Ministry (member)

MUDr. L. Macho, DrSc. - Cosmos Research and Peace Realization Committee (SR Counsel Government, member)- Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Normal and

Pathological Physiology of the Slovak Republic

MUDr. Vladimír Štrbák, DrSc.- Program Board of 6 FP ES priority 1 (appointed as delegate of Program Board

independent expert by SR Education Ministry) - Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Animal

Physiology and Etology of the Slovak Republic 2006

70

Ing. J. Brtko, DrSc.- Program Board of 6 FP ES „Integrating and Strengthening the European Research Area“ priority 5 (appointed as independent expert by SR Education Ministry)

Prof. PharmDr. D. Ježová, DrSc.- Slovak Literary Fund (Scientific and Computer Section, board member)

Prof. MUDr. I. Klimeš, DrSc.- Slovak Scientific Degree Granting Committee (SR Education Ministry, chairman)- Agency for Research and Development (APVV) - Committee for Medical Science (chairman)

RNDr. R. Kvetňanský, DrSc.- Slovak Commission for Research and Peaceful Use of Space at the Council for Science

and Technology of the Government of the SR (president)- High Level Space Policy Group- European Committee (delegate)- Program Board of 7 FP ES (appointed as delegate of Program Board independent expert by SR Education Ministry)- Report of Cosmos Activities in SR (participated in the elaboration for SR Regular

Mission in OSN– COPUOS Committee)

RNDr. A. Kiss, DrSc.- Board member of the committee for Doctor of Sciences (DSc.) habilitation in Animal

Physiology and Etology of the Slovak Republic

MUDr. P. Langer, DrSc.- Iodine Committee of SR Health Ministry (member)

MUDr. L. Macho, DrSc. - Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Normal and

Pathological Physiology of the Slovak Republic

MUDr. Vladimír Štrbák, DrSc.- Program Board of 6 FP ES, priority 1 (appointed as delegate of Program Board independent expert by SR Education Ministry)

- Chairman of the committee for Doctor of Sciences (DSc.) habilitation in Normal and Pathological Physiology of the Slovak Republic

iv. List of national awards and distinctions

2003

MUDr. R. Dunčko- Young Scientist Award of the Ministry of Education SR - Award of the Slovak Physiological Society for the year´s best paper of the year

Mgr. D. Gašperíková, CSc.- Guoth Prize from Slovak Medical Society for publication activity granted to young

scientists under age 35

MUDr. R. Imrich, PhD. - Prize from the Slovak Rheumatologic Society for a collection of papers

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Assoc. Prof. PharmDr. D. Ježová, DrSc. - National price Crystal Wing for Medicine and Science - Price of Slovak Physiological Society for the year’s best paper of the year- Core member of the Learned Society of SAS

Assoc. Prof. MUDr. I. Klimeš, DrSc. and Ing. E. Šeböková, DrSc. - PFIZER Prize of the Slovak Diabetes Society for the best paper of the year

RNDr. R. Kvetňanský, DrSc.- Core member of the Learned Society of SAS

MUDr. L. Macho, DrSc.- Memory Plaque Prize of the SAS in occasion of 50 years of SAS Anniversary

Mgr. L. Mičutková- Young Researchers Competition organized in occasion of 50 years of SAS

Anniversary up to age 35 (achieved the 1st position) MUDr. V. Štrbák, DrSc.- Jesenius Plaque Prize rewarded by the SAS for achievements in Medical Science - Gold Medal Prize rewarded by the Slovak Medical Society

2004

MUDr. R. Dunčko, PhD a Mgr. D. Macejová, PhD - Scientific Education Program (evaluated within the first 10 best participants)

MUDr. L. Macho, DrSc., MUDr. P. Langer, DrSc., MUDr. M. Vigaš, DrSc.- Elected as Emeritus members of the SAS Learned Society Assoc. Prof. MUDr. I. Klimeš, DrSc. - Elected as Regular member of the SAS Learned Society

2005

MUDr. Roman Dunčko, PhD.- Salutational Letter of the President of the SR for his outstanding research

achievements in 2004

Assoc. Prof.. PharmDr. D. Ježová, DrSc. - Invited by the board of the Slovak Physiological Society to present a hot research topic

on the 81. Physiological Days in Košice

Prof. MUD. Iwar Klimeš, DrSc., MUDr. Pavel Langer, DrSc.- Award from the Slovak Literary Fund for edition of textbook „General and Clinical

Endocrinology“- SERVIER and Slovak Diabetes Society joint price for the best publication 2004

RNDr. Richard Kvetňanský, DrSc.

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- Pribina's Cross Award of second grade from the President of the SR for outstanding achievements in sciences a social progress of SR.

- Slovak Literary Fund Prize for extraordinary amount of scientific citations

MUDr. Ladislav Macho, DrSc.- Propter Meritum Silver Medal Prize of the Slovak Medical Society with honorary

membership appraisal

2006

MUDr. P. Langer, DrSc., Prof. MUDr. I. Klimeš, DrSc., Ing. E. Šeböková, DrSc., Ing. A. Kočan, CSc., Prof. MUDr. M. Tajtáková, CSc., - Rewarded by the SAS award for scientific excellence achievements in collaboration

with universities of the SR

Prof. PharmDr. D. Ježová, DrSc. - Slovak Literary Fund Prize for the highest number of citations in the category of

Biological and Medical Sciences

Prof. MUDr. I. Klimeš, DrSc.

- Awarded by the „Medal of the SAS for Research Support“ of the SAS Chairmanship for long-standing management of the research development in different leading positions in the Slovak Medical Society, Slovak Scientific Committee for Granting of Scientific Degrees and Agencies for Research and Development Support.

RNDr. R. Kvetňanský, DrSc.– Award of the Slovak Literary Fund for lifelong subsidizing to the development of the

Slovak science at home and abroad.

MUDr. L. Macho, DrSc.

– Award of the Slovak Literary Fund for lifelong subsidizing to the development of the Slovak science at home and abroad.

MUDr. P. Langer, DrSc.– Award of the Slovak Literary Fund for lifelong subsidizing to the development of the

Slovak science at home and abroad.

MUDr. M. Vigaš, DrSc.– Award of the Slovak Literary Fund for lifelong subsidizing to the development of the

Slovak science at home and abroad.

Supplementary information and/or comments documenting international and

national status of the Organisation

73

Comments documenting the national status of the Organization

Institute of Experimental Endocrinology has been acknowledged and supported as Centre of Excellence of EU, and also as a Centre of excellence of the Slovak Academy of Sciences.The scientist of the IEE SAS besides the regular research activities also serve, during the years 2003-2006 in many important national scientific bodies, board, committees and editorial board of scientific journals. They were also involved in many activities in SR Government committees and were awarded for their outstanding work by many different prizes. Prof. MUDr. I. Klimeš, DrSc.served for several years as chairman of the Slovak Scientific Degree Granting Committee (Ministry of Education SR), chairman of the Slovak Endocrine Society and Board member of the Slovak Diabetes Society. RNDr. R. Kvetňanský,DrSc. and MUDr. L. Macho,DrSc. were involved in the Cosmos Activities of SR (participated in the elaboration of material for UNO – COPUOS Committee). RNDr. Kvetňanský was awarded by a prestigious Pribina´s Cross Award of second grade by the President of the SR for outstanding achievements in sciences and social progress of SR. Prof. PharmDr. D. Ježová, DrSc. is Board member of the Slovak Literary Fund (Scientific and Computer Section) . She was also also awarded by prestigious Crystal Wing Prize for outstanding achievements in Medical Sciences. MUDr. L. Macho, DrSc. was a member of the Slovak Commission for Research and Peaceful Use of Space – SR Counsel Government.We are proud of the achievements of our young scientists up to 35, MUDr. R. Dunčko, PhD., Mgr. D. Gašperíková, PhD., MUDr. R. Imrich, PhD., Mgr. L. Mičutková, PhD., Mgr. D. Macejová, PhD. All of them were awarded for outstanding achievements during PhD. Studies.

4. Project structure, research grants and other funding resources

International projects and funding

i. List of major projects within the European Research Area – 5th and 6th

Framework Programme of the EU, European Science Foundation, NATO, COST,

INTAS, CERN, etc. (here and in items below please specify: type of project, title,

grant number, duration, funding, responsible person in the Organisation and

his/her status in the project, e.g. coordinator, principal investigator,

investigator)

2003:

Active bilateral international projects [1] Interaction of immunomodulatory effect of prolactin and corticoid hormones. (MUDr.

R. Imrich, PhD.)Institution: Neuroendocrine Immunology Laboratory, Dept. of Pharmacology (FARC), Free University of Brussels, Belgium

[2] The role of hypothalamic neuropeptides and excitatory amino acids in neuroendocrine regulation in stress (Doc.PharmDr. D. Ježová, DrSc.) Institution: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

74

[3] The role of excitatory amino acids in dysfunction of brain capillary barrier(Doc.PharmDr. D. Ježová, DrSc.) Institution: Physiological Institute of the Czech Academy of Sciences, Prague, Czech Republic

[4] Effect of the specific brain areas lesion on regulation of the activity of symphaticoadrenal system in control and stressed rats(RNDr. R. Kvetňanský, DrSc.) Institution: Laboratory of Neuromorphology, Semmelweis University Medical School, Budapest, Hungary

[5] Neuroendocrine mechanismsof human organism adaptation in relation to condition of space flight

(RNDr. R. Kvetňanský, DrSc.) Institution: The State Research Centre of the Russian Federation, Russian Academy of Sciences, Moscow, Russia

Active multilateral international projects of the “International scientific/technical collaboration”

Projects of the 5 th Framework Programme

[1] Reduction of negative impact of environmental factors on human health (Centre of Excellence project)No.: ICA1-CT-2000-70008Coordinator: Assoc. Prof. PharmDr. Daniela Ježová, DrSc.Duration: 2002-2004Funding: Slovak Republic: 1,800.000,-SKK

European Commission: 42.500,-Euro

[2] Vitamin A, vitamin E and carotenoid status and metabolism during ageing: Functional and nutritional consequences

(RTD Action)No.: QLK1-CT-1999-00830Principal Investigator: Ing. Július Brtko, DrSc.Duration: 2000-2003Funding: Slovak Republic: 250.000,-SKK

European Commission: 12.900,-Euro

[3] Evaluating human health risk from low-dose and long-term PCB exposure(RTD Action)No.: QLK4-2000-00488Principal Investigator: MUDr. Pavel Langer, DrSc.Duration: 2001-2004Funding: Slovak Republic: 500.000,-SKK

European Commission: 0,-Euro

[4] Dysregulation of endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticisers

(RTD Action)No.: QLK4-CT-2002-02637Principal Investigator: RNDr. Mária Ficková, CSc.Duration: 2003-2006Funding: Slovak Republic: 250.000,-SKK

European Commission: 62.738,-Euro

[5] Construction of a new Drosophila duplication collection

75

(RTD Action)No.: QLRI-CT2001-02841Principal Investigator: RNDr. Robert Farkaš, CSc.Duration: 2003-2004Funding: Slovak Republic: 176.000,-SKK

European Comission: 24.500,-Euro

Multilateral projects (COST, INTAS, EUREKA, ESPIRIT, PHARE, NATO, UNESCO, CERN, IAEA, ESF and others)

[1] Genes in Control of Apoptosis during Drosophila metamorphosis (NATO project)No.: LST.CLG-977559Principal Investigator: RNDr. Robert Farkaš, CSc.Duration: 2002-2004Funding: Slovak Republic: 51.000,-SKK

NATO: 5.000,-Euro

[2] Fatty acid oxidation and insulin resistance(COST)No.: COST B17 Principal Investigator: Ing. Elena Šeböková, DrSc., Assoc. Prof.MUDr. Iwar Klimeš, DrSc.Duration: 2000-2005Funding: Slovak Republic: 0,-SKK

European Commission: 0,-Euro

ii. List of other international projects incl. funding

[1] Function and molecular interactions of LAMMER kinase(USA-Slovak Republic project)No.: 029/2001Principal Investigator: RNDr. Robert Farkaš, CSc.Duration: 2000-2004Funding: Slovak Republic: 300.000,-SKK

USA: 10.000,-USD

[2] Ethanol and cell swelling induced peptide secretion: intracellular signalling and regulation

(USA-Slovak Republic project)No.: 172001Principal Investigator: MUDr. Vladimír Štrbák, DrSc.Duration: 2000-2005Funding: Slovak Republic: 300.000,-SKK

[3] Stressor-specific regulation of catecholamine biosynthetic enzyme gene expression

(USA-Slovak Republic project)No.: 002/2001Principal Investigator: RNDr. Richard Kvetňanský, DrSc.Duration: 2000-2005Funding: Slovak Republic: 300.000,-SKK

76

[4] Design of new precursors of small biologically active substances(Czech Republic-Slovak Republic project)No.: 191/073Principal Investigator: Ing. Štefan Zorad, CSc.Duration: 2002-2003Funding: Slovak Republic: 23.000,-SKK

iii. List of other important projects and collaborations without direct funding

[1] Prevention by nutrition - The effects of fatty acid chain length on postprandial metabolism of lipids and glycides, and the biological effect of insulinCoordinators: Ing. E. Šeböková, DrSc. and Assoc. Prof..MUDr. I. Klimeš, DrSc. Prtners: Prof. J. Schrezenmeir (Kiel), Prof. S. Woffram (Kiel), Dr. M. Pfeiffer (Kiel), Dr. E. Trautwein (UNILEVER, Netherlands), Dr. S. Wein (Bratislava)Institutions: (1) Institute of Physiology and Biochemistry of Nutrition, University of Kiel, Germany; (2) Institute of Animal Nutrition and Metabolism - Christian Albrechts Uiversity of Kiel, Germany

[2] Slovakia PCB exposures and early childhood development (project NIH„SPEECD“)Partners at the Institute: MUDr. P. Langer, DrSc., Assoc. Prof. MUDr. I. Klimeš, DrSc., Ing. E. Šeböková, DrSc., Institutions: University of California at Davis, Davis, CA, USA

[3] Interaction of immunomodulatory effect of prolactin and corticoid hormones. (MUDr. R. Imrich, PhD.)Institution: Neuroendocrine Immunology Laboratory, Dept. of Pharmacology (FARC), Free University of Brussels, Belgium

[4] Mechanisms of neuroendocrine activation under different stress conditions physiological and genetic approaches. (Assoc. Prof.. PharmDr. D. Ježová, DrSc.)

Institution: Developmental Endocrinology Branch, NICHD, NIH, Bethesda, USA

[5] Analysis of relationships between various physiological parameters in man and behaviour in stress.

Institution: Gerstner Laboratory, Dept. of Cybernetics FEL ČVUT, Prague, Czech Republic(1) Qualitative and quantitative changes in Fos induction in the rat deep cerebellar and vestibular nuclei after central administration of colchicines. (RNDr. A. Kiss, DrSc.)(2) Hypertonic saline and immobilization induced Fos-expression in mouse brain catecholaminergic cell groups: colocalization with tyrosine hydroxylase (TH) and neuropeptide Y (NPY). (RNDr. A. Kiss, DrSc.)(3) Serotoninergic stimulation of the rat hypothalamo-pituitary-adrenal (HPA) axis: interaction between 5-HT1a and 5-HT2a receptors. (RNDr. A. Kiss, DrSc.)Institution: Department of Molecular Anatomy and Physiology, Neurosearch A/S, Ballerup, Denmark

[6] Changes of neurotransmitter system by the PET technique in man and in laboratory animals with focus on adrenal cortex tumours. (RNDr. R. Kvetňanský, DrSc.) Institution: Pediatric and Reproductive Endocrinology Branch, National Institute of Child

and Human Development, NIH, Bethesda, USA

[7] Effects of expression and translation transcription factors involved in the regulation of PNMT expression in stress. (RNDr. R. Kvetňanský, DrSc.) Institution: Laboratory of Molecular and Developmental Neurobiology, Department of Psychiatry, Harvard Medical School, Belmont, Massachussetts, USA

77

[8] Regulation of the factor liberation responsible for prolactin release in stress. (RNDr. R. Kvetňanský, DrSc.) Institution: Neuroendocrine Research Laboratory, Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest, Hungary

[9] Catecholamines and their metabolites during bedrest in physically fit subjects. (RNDr. R. Kvetňanský, DrSc.) Institution: Laboratory of Environmental Physiology, Faculty of Medicine Lyon Grange-Blanche, Lyon, France

[10] The effect of the social hierarchy on expression of genes responsible for synthesis of catecholamines in adrenal cortex. (RNDr. R. Kvetňanský, DrSc.)

Institution: Rutgers University, New Jersey, USA

[11] The effect of limited muscular activity on endocrine, metabolic and cardiovascular response in man. (MUDr. M. Vigaš, DrSc.)

Institution: Department of Applied physiology, Medical Research Centre of the Polish Academy of Sciences, Warsaw, Poland

2004

i. List of major projects within the European Research Area – 5th and 6th

Framework Programme of the EU, European Science Foundation, NATO, COST,

INTAS, CERN, etc. (here and in items below please specify: type of project, title,

grant number, duration, funding, responsible person in the Organisation and his/her

status in the project, e.g. coordinator, principal investigator, investigator)

Active bilateral international projects

[1] Interaction of immunomodulatory effect of prolactin and corticoid hormones. (MUDr. R. Imrich, PhD.)

Institution: Neuroendocrine Immunology Laboratory, Dept. of Pharmacology (FARC), Free University of Brussels, Belgium

[2] The role of hypothalamic neuropeptides and excitatory amino acids in neuroendocrine regulation in stress (Assoc. Prof..PharmDr. D. Ježová, DrSc.) Institution: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

[3] Effect of the specific brain areas lesion on regulation of the activity of symphaticoadrenal system in control and stressed rats(RNDr. R. Kvetňanský, DrSc.) Institution: Laboratory of Neuromorphology, Semmelweis University Medical School, Budapest, Hungary

[4] Neuroendocrine mechanismsof human organism adaptation in relation to condition of space flight (RNDr. R. Kvetňanský, DrSc.) Institution: The State Research Centre of the Russian Federation, Russian Academy of Sciences, Moscow, Russia

78

Active multilateral international projects of the “International scientific/technical collaboration”

Projects of the 5 th Framework Programme

[1] Reduction of negative impact of environmental factors on human health (Centre of Excellence project)No.: ICA1-CT-2000-70008Coordinator: Assoc. Prof. PharmDr. Daniela Ježová, DrSc.Duration: 2002-2004Funding: Slovak Republic:

European Commission: 99.000,-Euro

[2] Evaluating human health risk from low-dose and long-term PCB exposure(RTD Action)No.: QLK4-2000-00488Principal Investigator: MUDr. Pavel Langer, DrSc.Duration: 2001-2004Funding: Slovak Republic: 500.000,-SKK

European Commission: 0,-Euro

[3] Dysregulation of endogenous steroid metabolism alters neuronal and reroductive system development: effects of environmental plasticisers

(RTD Action)No.: QLK4-CT-2002-02637Principal Investigator: RNDr. Mária Ficková, CSc.Duration: 2003-2006Funding: Slovak Republic: 250.000,-SKK

European Commission: 37.196,-Euro

[4] Construction of a new Drosophila duplication collection(RTD Action)No.: QLRI-CT2001-02841Principal Investigator: RNDr. Robert Farkaš, CSc.Duration: 2003-2004Funding: Slovak Republic: 176.000,-SKK

European Commission: 24.500,-Euro

Multilateral projects (COST, INTAS, EUREKA, ESPIRIT, PHARE, NATO, UNESCO, CERN, IAEA, ESF and others)

Genes in Control of Apoptosis during Drosophila metamorphosis (NATO project)No.: LST.CLG-977559Principal Investigator: RNDr. Robert Farkaš, CSc.Duration: 2002-2004Funding: Slovak Republic: 51.000,-SKK

NATO: 5.000,-Euro

Fatty acid oxidation and insulin resistance(COST)No.: COST B17 Principal Investigator: Ing. Elena Šeböková, DrSc., Assoc. Prof. MUDr. Iwar Klimeš, DrSc.Duration: 2000-2005Funding: Slovak Republic: 0,-SKK

European Commission: 0,-Euro

79

ii. List of other international projects incl. funding

[1] Function and molecular interactions of LAMMER kinase(USA-Slovak Republic project)No.: 029/2001Principal Investigator: RNDr. Robert Farkaš, CSc.Duration: 2000-2004Funding: Slovak Republic: 300.000,-SKK

USA: 10.000,-USD

[2] Ethanol and cell swelling induced peptide secretion: intracellular signalling and regulation(USA-Slovak Republic project)No.: 172001Principal Investigator: MUDr. Vladimír Štrbák, DrSc.Duration: 2000-2005Funding: Slovak Republic: 300.000,-SKK

[3] Stressor-specific regulation of catecholamine biosynthetic enzyme gene expression

(USA-Slovak Republic project)No.: 002/2001Principal Investigator: RNDr. Richard Kvetňanský, DrSc.Duration: 2000-2005Funding: Slovak Republic: 300.000,-SKK

[4] Central Mechanisms regulation of the activity of catecholaminergic system(Serbia and Monte Negro-Slovak Republic project)No.: 2 SR+CHPrincipal Investigator: RNDr. Richard Kvetňanský, DrSc.Duration: 2004-2006Funding: Slovak Republic: 77.000,-SKK

[5] Slovakia PCB exposures and early childhood development (NIH grant „SPEECD“)Principal Investigators: Assoc. Prof. MUDr. Iwar Klimeš, DrSc., MUDr. P. Langer, DrSc., Ing. Elena Šeböková, DrSc.,Duration: 2004-2006Funding: Slovak Republic: 0,-SKK

European Commission: 0,-Euro

iii. List of other important projects and collaborations without direct funding

[1] Prevention by nutrition - The effects of fatty acid chain length on postprandial metabolism of lipids and glycides, and the biological effect of insulinCoordinators: Ing. E. Šeböková, DrSc. and Assoc. Prof. MUDr. I. Klimeš, DrSc. Partners: Prof. J. Schrezenmeir (Kiel), Prof. S. Woffram (Kiel), Dr. M. Pfeiffer (Kiel), Dr. E. Trautwein (UNILEVER, Netherlands), Dr. S. Wein (Bratislava)Institutions: (1) Institute of Physiology and Biochemistry of Nutrition, University of Kiel, Germany; (2) Institute of Animal Nutrition and Metabolism - Christian Albrechts University of Kiel, Germany

[2] Slovakia PCB exposures and early childhood development (project NIH„SPEECD“)Partners at the Institute: Assoc. Prof. MUDr. I. Klimeš, DrSc., Ing. E. Šeböková, DrSc., MUDr. P. Langer, DrSc.

80

Institutions: University of California at Davis, Davis, CA, USA

[3] Interaction of immunomodulatory effect of prolactin and corticoid hormones. (MUDr. R. Imrich, PhD.)Institution: Neuroendocrine Immunology Laboratory, Dept. of Pharmacology (FARC), Free University of Brussels, Belgium

[4] Analysis of relationships between various physiological parameters in man and behaviour in stress. (Assoc. Prof. PharmDr. D. Ježová, DrSc.)Institution: Gerstner Laboratory, Dept. of Cybernetics FEL ČVUT, Prague, Czech Republic

[5] Study of the hormonal changes in relation to possible antidepressive effects of pharmaceutical preparations (Assoc. Prof. PharmDr. D. Ježová, DrSc.)Institution: Institute of Pharmacology, Medical Faculty of Masaryk University, Brno, Czech Republic

[6] (1) Qualitative and quantitative changes in Fos induction in the rat deep cerebellar and vestibular nuclei after central administration of colchicines. (RNDr. A. Kiss, DrSc.) (2) Hypertonic saline and immobilization induced Fos-expression in mouse brain catecholaminergic cell groups: colocalization with tyrosine hydroxylase (TH) and neuropeptide Y (NPY). (RNDr. A. Kiss, DrSc.)(3) Serotoninergic stimulation of the rat hypothalamo-pituitary-adrenal (HPA) axis: interaction between 5-HT1a and 5-HT2a receptors. (RNDr. A. Kiss, DrSc.)Institution: Department of Molecular Anatomy and Physiology, Neurosearch A/S, Ballerup, Denmark

[7] Changes of neurotransmitter system by the PET technique in man and in laboratory animals with focus on adrenal cortex tumours. (RNDr. R. Kvetňanský, DrSc.) Institution: Paediatric and Reproductive Endocrinology Branch, National Institute of Child and Human Development, NIH, Bethesda, USA

[8] Effects of expression and translation transcription factors involved in the regulation of PNMT expression in stress. (RNDr. R. Kvetňanský, DrSc.)

Institution: Laboratory of Molecular and Developmental Neurobiology, Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA

[9] Regulation of the factor liberation responsible for prolactin release in stress. (RNDr. R. Kvetňanský, DrSc.) Institution: Neuroendocrine Research Laboratory, Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest, Hungary

[10] Study of the changes of the catecholaminergic system in rat brain and heart (RNDr. R. Kvetňanský, DrSc.)

Institution: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, USA

[11] The effect of the social hierarchy on expression of genes responsible for synthesis of catecholamines in adrenal cortex. (RNDr. R. Kvetňanský, DrSc.)

Institution: Rutgers University, New Jersey, USA

[12] DNA diagnostics of neonatal diabetes (Assoc.Prof. MUDr.I.Klimeš,DrSc.) Institution: Institute of Biomedical Research, Penninsula Medical School, Exeter, UK

[13] Structure – function studies in neonatal diabetes (Assoc.Prof. MUDr. I.Klimeš,DrSc.) Institution: University Laboratory of Physiology, Oxford, UK

[14] Subclinical inflammation in adipose tissue (Mgr. D. Gašperíková, CSc.)

81

Institution: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany

2005:i. List of major projects within the European Research Area – 5th and 6th Framework

Programme of the EU, European Science Foundation, NATO, COST, INTAS, CERN,

etc. (here and in items below please specify: type of project, title, grant number,

duration, funding, responsible person in the Organisation and his/her status in the

project, e.g. coordinator, principal investigator, investigator)

Active bilateral international projects

[1] The role of hypothalamic neuropeptides and excitatory amino acids in neuroendocrine regulation in stress (Assoc. Prof.PharmDr. D. Ježová, DrSc.) Institution: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

[2] Effect of stimulation of alpha2 adrenergic receptors on activity of oxytocinergical neurons of hypothalamus in Brattleboro rats(RNDr. A.Kiss, DrSc.) Institution: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

Active multilateral international projects of the “International scientific/technical collaboration”

Projects of the 5 th Framework Programme

[1] Dysregulation of endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticisers

(RTD Action)No.: QLK4-CT-2002-02637Principal Investigator: RNDr. Mária Ficková, CSc.Duration: 2003-2006Funding: Slovak Republic: 250.000,-SKK

European Commission: 16.287,-Euro

Multilateral projects (COST, INTAS, EUREKA, ESPIRIT, PHARE, NATO, UNESCO, CERN, IAEA, ESF and others)

[1] Fatty acid oxidation and insulin resistance(COST)No.: COST B17 Principal Investigator: Ing. Elena Šeböková, DrSc., Assoc. Prof.MUDr. Iwar Klimeš, DrSc.Duration: 2000-2005Funding: Slovak Republic: 0,-SKK

European Commission: 0,-Euro ii. List of other international projects incl. funding

[1] Function and molecular interactions of LAMMER kinase(USA-Slovak Republic project)No.: 029/2001

82

Principal Investigator: RNDr. Robert Farkaš, CSc.Duration: 2000-2004/5Funding: Slovak Republic: 300.000,-SKK

USA: 10.000,-USD

[2] Slovakia PCB exposures and early childhood development (NIH grant „SPEECD“)Principal Investigators: Assoc. Prof.MUDr. Iwar Klimeš, DrSc., MUDr. P. Langer, DrSc., Ing. Elena Šeböková, DrSc.,Duration: 2004-2006Funding: Slovak Republic: 136.000-SKK

[3] Ethanol and cell swelling induced peptide secretion: intracellular signalling and regulation

(USA-Slovak Republic project)No.: 172001Principal Investigator: MUDr. Vladimír Štrbák, DrSc.Duration: 2000-2005Funding: Slovak Republic: 300.000,-SKK

[4] Stressor-specific regulation of catecholamine biosynthetic enzyme gene expression(USA-Slovak Republic project)No.: 002/2001Principal Investigator: RNDr. Richard Kvetňanský, DrSc.Duration: 2000-2005Funding: Slovak Republic: 300.000,-SKK

[5] Central Mechanisms regulation of the activity of catecholaminergic system(Serbia and Monte Negro-Slovak Republic project)No.: 2 SR+CHPrincipal Investigator: RNDr. Richard Kvetňanský, DrSc.Duration: 2004-2006Funding: Slovak Republic: 60.000,-SKK

[6] Environmental influences on hormone release during stress in humans: continuation of previous common studies

(Austria-Slovak Republic project)No.: SK-04-BA-009Principal Investigator: Assoc. Prof.PharmDr. Daniela Ježová, DrSc. Duration: 2005Funding: SAIA: 5.000,-Euro

[7] Environmental stimuli and neuronal plasticity(Greece-Slovak Republic project)No.: 005-14768/1 CD-26497Principal Investigator: Assoc. Prof.PharmDr. Daniela Ježová, DrSc. Duration: 2005Funding: Ministry of Education, SR: 63.000,-SKK

iii. List of other important projects and collaborations without direct funding

[1] (1) Effect of benzodiazepines receptor agonists on the hypothalamic pituitary adrenocortical axis. (RNDr. A. Kiss, DrSc.)(2) To reveal the role of α2 –adrenergic receptors in the regulation of the hypothalamic magnocellular system under normal and hyperosmotic conditions (RNDr. A. Kiss, DrSc.)

83

(3) Study the effect of acute treatments with typical and atypical antipsychotics on the activity of hypocretin synthesizing neurons in the lateral hypothalamus and oxytocin producing neurons in the PVN of rats. (RNDr. A. Kiss, DrSc.)

Institution: Department of Molecular Anatomy and Physiology, Neurosearch A/S, Ballerup, Denmark

[2] Changes of neurotransmitter system by the PET technique in man and in laboratory animals with focus on adrenal cortex tumours. (RNDr. R. Kvetňanský, DrSc.) Institution: Pediatric and Reproductive Endocrinology Branch, National Institute of Child and Human Development, NIH, Bethesda, USA

[3] Effects of expression and translation transcription factors involved in the regulation of PNMT expression in stress. (RNDr. R. Kvetňanský, DrSc.)

Institution: Laboratory of Molecular and Developmental Neurobiology, Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA

[4] Regulation of the factor liberation responsible for prolactin release in stress. (RNDr. R. Kvetňanský, DrSc.)

Institution: Neuroendocrine Research Laboratory, Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest, Hungary

[5] The effect of specific areas lesions on regulation of the activity of sympaticoadrenal system in control and stressed rats. (RNDr. R. Kvetňanský, DrSc.)

Institution: Laboratory of Neuromorphology, Semmelweis University, Budapest, Hungary

[6] Study of the changes of the catecholaminergic system in rat brain and heart (RNDr. R. Kvetňanský, DrSc.)

Institution: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, USA

[7] The effect of the social hierarchy on expression of genes responsible for synthesis of catecholamines in adrenal cortex. (RNDr. R. Kvetňanský, DrSc.)

Institution: Rutgers University, New Jersey, USA

[8] Effect of retinoid signalling system on immune response (Ing. J. Brtko, DrSc.)Institution: University of Salzburg, Salzburg, Austria

[9] Changes of intracellular calcium in cells secreting insulin (MUDr. V. Štrbák, DrSc.)Institution: Bogolometz Institute of Physiology, Kiev, Ukraine

[10] The role of glucose in activation of ICIn membrane channel (MUDr. V. Štrbák, DrSc.)Institutions: Institute of Physiology, Paracelsus Private Medical University, Salzburg, Austria; Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria; Universita degli Studi di Milano, Milano, Italy

[11] Relation of Angiotensin II and adiponectine (MUDr. V. Štrbák, DrSc.)Institution: NIH, Bethesda, USA

[12] DNA diagnostics of various forms of neonatal diabetes (Assoc. Prof. MUDr. I. Klimeš, DrSc.)

Institution: Institute of Biomedical Research, Penninsula Medical School, Exeter, UK

[13] Structure – function studies in neonatal diabetes (Assoc.Prof.MUDr. I. Klimeš, DrSc.)

Institution: University Laboratory of Physiology, Oxford, UK

[14] Subclinical inflammation in adipose tissue (Mgr. D. Gašperíková, CSc.)Institution: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes

Center, Düsseldorf, Germany

84

2006:

i. List of major projects within the European Research Area – 5th and 6th Framework

Programme of the EU, European Science Foundation, NATO, COST, INTAS, CERN,

etc. (here and in items below please specify: type of project, title, grant number,

duration, funding, responsible person in the Organisation and his/her status in the

project, e.g. coordinator, principal investigator, investigator)

Active bilateral international projects

[1] The role of hypothalamic neuropeptides and excitatory amino acids in neuroendocrine regulation in stress (Assoc. Prof.PharmDr. D. Ježová, DrSc.) Institution: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

[2] Effect of benzodiazepines receptor agonists (Zolpidem) on the activity of magnocellular population of hypothalamic neurons (RNDr. A.Kiss, DrSc.) Institutions: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary and Department of Translational Neuroscience, NeuroSearch AS, Ballerup, Denmark

Active multilateral international projects of the “International scientific/technical collaboration”

Projects of the 5 th Framework Programme

[1] Dysregulation of endogenous steroid metabolism alters neuronal and reproductive system development: effects of environmental plasticisers

(RTD Action)No.: QLK4-CT-2002-02637Principal Investigator: RNDr. Mária Ficková, CSc.Duration: 2003-2006Funding: Slovak Republic: 250.000,-SKK

European Commission: 16.287,-Euro

Projects of the 6 th Framework Programme

[1] Chemical contaminants in the food chain(NoE)No.: FOOD-CT-2004-506319Principal Investigator: Ing. Július Brtko, DrSc.Duration: 2006-2009Funding: Slovak Republic: 0,-SKK

European Commission: 25.000,-Euro

[2] The Danubian Biobank Initiative: Towards Information-Based Medicine(SSA)No.:FP6 - 018822Principal Investigator: Prof.MUDr. Iwar Klimeš, DrSc.Duration: 2006-2009Funding: Slovak Republic: 0,-SKK

European Commission: 20.255,-Euro

85

ii. List of other international projects incl. funding

[1] Environmental stimuli and neuronal plasticity(Greece-Slovakia)No.: CD-2005-14768/16497Principal Investigator: Prof.PharmDr. Daniela Ježová, DrSc.Duration: 2006-Funding: Slovak Republic: 80.000,-SKK

[2] Evaluation of stress, brain and cardiovascular system(Austria-Slovakia)No.: SK-05/06-BA-007Principal Investigator: Prof.PharmDr. Daniela Ježová, DrSc.Duration: 2006-Funding: 3.000,-Euro

[3] Transmembrane interactions in cellular signalling

(France-Slovakia: STEFANIK)No.: SK-05/06-BA-007Principal Investigator: RNDr. Mária Ficková, CSc.Duration: 2006-2007Funding: Slovak Republic: 80.000,-SKK

[4] Effect of the vagal nerve stimulation on tumor development and progression(The Netherlands-Slovakia)No.: Principal Investigator: MUDr. Boris Mravec, PhD.Duration: 2006-2007Funding: Cyberonics grant 9.000,-Euro

iii. List of other important projects and collaborations without direct funding

[1] Changes of neurotransmitter system by the PET technique in man and in laboratory animals with focus on adrenal cortex tumours. (RNDr. R. Kvetňanský, DrSc.)

Institution: Pediatric and Reproductive Endocrinology Branch, National Institute of Child and Human Development, NIH, Bethesda, USA

[2] Effects of expression and translation transcription factors involved in the regulation of PNMT expression in stress. (RNDr. R. Kvetňanský, DrSc.)

Institution: Laboratory of Molecular and Developmental Neurobiology, Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA

[3] Regulation of the factor liberation responsible for prolactin release in stress. (RNDr. R. Kvetňanský, DrSc.)

Institution: Neuroendocrine Research Laboratory, Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest, Hungary

[4] The effect of specific areas lesions on regulation of the activity of sympathoadrenal system in control and stressed rats. (RNDr. R. Kvetňanský, DrSc.)

Institution: Laboratory of Neuromorphology, Semmelweis University, Budapest, Hungary

[5] Study of the changes of the catecholaminergic system in rat brain and heart (RNDr. R. Kvetňanský, DrSc.)

Institution: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, USA

86

[6] The effect of the social hierarchy on expression of genes responsible for synthesis of catecholamines in adrenal cortex. (RNDr. R. Kvetňanský, DrSc.)

Institution: Rutgers University, New Jersey, USA

[7] Effect of retinoid signalling system on immune response (Ing. J. Brtko, DrSc.)Institution: University of Salzburg, Salzburg, Austria

[8] Changes of intracellular calcium in cells secreting insulin (MUDr. V. Štrbák, DrSc.)Institution: Bogolometz Institute of Physiology, Kiev, Ukraine

[9] The role of glucose in activation of ICIn membrane channel (MUDr. V. Štrbák, DrSc.)Institutions: Institute of Physiology, Paracelsus Private Medical University, Salzburg, Austria; Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria; Universita degli Studi di Milano, Milano, Italy

[10] Relation of Angiotensin II and adiponectine (MUDr. V. Štrbák, DrSc.)Institution: NIH, Bethesda, USA

[11] DNA diagnostics of various forms of neonatal diabetes (Prof.MUDr. I. Klimeš, DrSc.) Institution: Institute of Biomedical Research, Penninsula Medical School, Exeter, UK

[12] Structure – function studies in neonatal diabetes (Prof. MUDr. I. Klimeš, DrSc.) Institution: University Laboratory of Physiology, Oxford, UK

[13] Subclinical inflammation in adipose tissue (Mgr. D. Gašperíková, CSc.)Institution: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany

National projects and funding

i. List of projects supported by the Agency for the Promotion of Research and

Development (APVV/APVT), National Research Programmes, and their funding

National Centres of Excellence:

2006: Centrum of Excellence for the research of neuroendocrine mechanisms in the pathogenesis of major diseases (acronym CENDO)

APVT:

2003: 1) APVT 21-008602 - Interaction of central and local hormonal and immune factors in

the pathogenesis and development of rheumatoid arthritis

2) APVT 20-016002 - Immobilized biological systems: Regulation of transport of nanoscale bioactive substances through well-defined polymer membranes in biotechnology and biomedicine

2004: 1) APVT 21-008602 - Interaction of central and local hormonal and immune factors in

the pathogenesis and development of rheumatoid arthritis

87

2) APVT 51-040602 - Hormonal regulation of gene expression for enzymes of lipid metabolism in the adipose tissue of obese and insulin resistant subjects

3) APVT 51-027402 - Genes involved in programmed cell death

4) APVT 20-016002 - Immobilized biological systems: Regulation of transport of nanoscale bioactive substances through well-defined polymer membranes in biotechnology and biomedicine

2005: 1) APVT 51-027402 - Genes involved in programmed cell death in Drosophila

2) APVV 51-040602 - Hormonal regulation of gene expression for enzymes of lipid metabolism in the adipose tissue of obese and insulin resistant subjects

3) APVT 21-008602 - Interaction of central and local hormonal and immune factors in the pathogenesis and development of rheumatoid arthritis

4) APVT 20-016002 - Immobilized biological systems: Regulation of transport of nanoscale bioactive substances through well-defined polymer membranes in biotechnology and biomedicine

2006: 1) APVT 51-027402 - Genes involved in programmed cell death in Drosophila

2) APVT 51-040602 - Hormonal regulation of gene expression for enzymes of lipid metabolism in the adipose tissue of obese and insulin resistant subjects

3) LPP-0194-06 - Education of young specialists in the field of the neurobiological basis of mental disorders

4) APVV 51-017905 - Molecular mechanisms of new drugs influencing oxidative stress – important ethiopathogenetic factor of numerous diseases

5) APVV-51-014205 - DNA analysis of monogenic forms of diabetes in Slovakia

National Research Programmes:

2003: 2003 SP 51/028 08 00/028 08 02 - Genomics of cardiovascular diseases for healthier human population

2004: 2003 SP 51/028 08 00/028 08 02-2004 - Genomics of cardiovascular diseases for healthier human population

2005: 2003 SP 51/028 08 00/028 08 02-2005 - Genomics of cardiovascular diseases for healthier human population

88

National Diabetes Program:

2003: Screening of MODY and MIDD

2004: Screening of DM-2, MODY-3 and MIDD

Projects supported by the Slovak Ministry of Health:

2006:

1) MZ 2005/15-NEDU-01 - Introduction of DNA diagnostics and the screening of monogenic forms of diabetes in Slovakia

2) MZ 2005/20- NURCH-04 - The effect of chronic inflammation on metabolism in rheumatic diseases

Projects supported by European Social Fund:

2005: 1) 13120200056 - Health of inhabitants of Bratislava region – contribution to better

coping with stress based on results of top research

2) 13120200067 - Positron emission tomography for small laboratory animals, introduction of the method in research and evaluation of new drugs in Centre of Excellence of the EU

2006: 1) 13120200056 - Health of inhabitants of Bratislava region – contribution to better

coping with stress based on results of top research

2) 13120200067 - Positron emission tomography for small laboratory animals, introduction of the method in research and evaluation of new drugs in Centre of Excellence of the EU

VEGA:

2003: 1) 2/2090/23 - Studies of the regulation of gene expression of enzymes of

catecholaminergic system and their modulation by transcription factors in mammals due to the stress

2) 2/2007/23 - Simulation of stress states occurring in daily life: type of stress stimuli and neuroendocrine function

3) 2/3150/23 - The role of neuroendocrine mechanisms in the insulin resistance and hypertension in human

4) 2/3190/23 - Contribution to revealing the role of local renin – angiotensin systems in adipose tissue, spleen, lymphocytes and mammary gland carcinoma

89

5) 2/1098/23 - The role of transmembrane segment of membrane receptors in the mechanism of their effect

6) 2/3191/23 - Traditional and unconventional mechanisms of regulation of peptide secretion

7) 2/3099/23 - Endocrine disruptors /polychlorinated biphenyls and pesticides/ and frequency of diabetes and markers of mammary gland cancer in inhabitants of polluted areas

8) 2/2070/23 - In vivo transfection of DNA vaccines in relation to biological effects of retinoic acids in normal and neoplastic tissue of mammary gland in rat

9) 2/3052/23 - Xenoestrogens related disorders in female reproductive system

10) 2/3025/23 - Molecular-genetic analysis of the function and expression of hormonally responsive malate dehydrogenases in Drosophila melanogaster

11) 1/8287/23 - Offspring of diabetic mothers in adolescence

2004: 1) 2/2007/23 - Simulation of stress states occurring in daily life: type of stress stimuli

and neuroendocrine function

2) 2/2070/22 - In vivo transfection of DNA vaccines in relation to biological effects of retinoic acids in normal and neoplastic tissue of mammary gland in rat

3) 2/2090/24 - Studies of the regulation of gene expression of enzymes of catecholaminergic system and their modulation by transcription factors in mammals due to the stress

4) 2/3025/23 - Molecular-genetic analysis of the function and expression of hormonally responsive malate dehydrogenases in Drosophila melanogaster

5) 2/3052/23 - Xenoestrogens related disorders in female reproductive system

6) 2/3099/23 - Endocrine disruptors /polychlorinated biphenyls and pesticides/ and frequency of diabetes and markers of mammary gland cancer in inhabitants of polluted areas

7) 2/3150/23 - The role of neuroendocrine mechanisms in the insulin resistance and hypertension in human

8) 2/3190/23 - Contribution to revealing the role of local renin – angiotensin systems in adipose tissue, spleen, lymphocytes and mammary gland carcinoma

9) 2/3191/23 - Traditional and unconventional mechanisms of regulation of peptide secretion

10) 2/4030/4 - Mechanism of protective and harmful effect of alcohol on hormonally controlled metabolism of adipose tissue

11) 2/4128/4 - Development of experimental arthritis in rats under different nutritional conditions: the involvement of leptin

90

2005: 1) 2/5017/5 - Character, function and role of transcription factors inducible by

biologically active hydrophobic molecules in rat mammary gland

2) 2/3025/23 - Molecular-genetic analysis of the function and expression of hormonally responsive malate dehydrogenases in Drosophila melanogaster

3) 2/4030/4 - Mechanism of protective and harmful effect of alcohol on hormonally controlled metabolism of adipose tissue

4) 2/5064/5 - Neuroendocrine mechanisms in relation to mental state and to the effects of psychotropic drugs

5) 2/4128/4 - Development of experimental arthritis in rats under different nutritional conditions: the involvement of leptin

6) 2/3099/23 - Endocrine disruptors /polychlorinated biphenyls and pesticides/ and frequency of diabetes and markers of mammary gland cancer in inhabitants of polluted areas

7) 2/5125/25 - Transcriptional mechanisms of stress-induced changes in gene expression of catecholamine biosynthetic enzymes and their receptors

8) 2/5090/25 - Study on structure – activity relationship of insulin analogs modified in the C-terminus of the insulin B-chain

9) 2/3052/23 - Xenoestrogens related disorders in female reproductive system

10) 2/3191/23 - Traditional and unconventional mechanisms of regulation of peptide secretion

11) 2/3150/24 - The role of neuroendocrine mechanisms in the insulin resistance and hypertension in human

12) 2/3190/23 - Contribution to revealing the role of local renin – angiotensin systems in adipose tissue, spleen, lymphocytes and mammary gland carcinoma

2006: 1) 2/5017/5 - Character, function, and role of transcription factors inducible by

biologically active hydrophobic molecules in rat mammary gland

2) 2/4030/26 - Mechanism of protective and harmful effect of alcohol on hormonally controlled metabolism of adipose tissue

3) 1/1185/26 - Secondary metabolites of selected plants species influencing apoptosis

4) 2/5064/5 - Neuroendocrine mechanisms in relation to mental state and the effects of psychotropic drugs

5) 2/4128/4 - Development of experimental arthritis in rats under different nutritionalconditions: role of leptin

91

6) 2/5125/26 - Transcriptional mechanisms of stress-induced changes in gene expression of catecholamine biosynthetic enzymes and their receptors

7) 2/6171/26 - Effect of binary mixtures of xenoestrogens on ovarian intrafollicular processes

8) 2/6158/26 - Novel signaling pathway for swelling-induced hormone secretion

9) 2/6157/27 - Adrenal gland and sympathetic nervous system in the pathogenesis of rheumatic diseases

10) 2/5090/25 - Study on structure – activity relationship of insulin analogs modified in the C-terminus of the insulin B-chain

ii. Number of projects supported by the Scientific Grant Agency of the Slovak

Academy of Sciences and the Ministry of Education (VEGA) for each year, and

their funding

VEGA 2003 2004 2005 2006

number 11 11 12 10

funding (millions of SKK) 1,261 1,201 1,372 1,239

Summary of funding from external resources

External resources 2003 2004 2005 2006 total average

external resources (millions of SKK) 14,581 16,068 14,141 14,252 22,580 14,761

external resources transfered to coooperating research organisations (millions of SKK)

0,000 0,000 0,000 0,000 0,000 0,000

ratio between external resources and total salary budget

1,186 1,169 0,962 0,905 4,222 1,056

overall expenditures from external as well as institutional resources(millions of SKK)

15,842 17,269 15,513 15,719 64,343 16,086

Supplementary information and/or comments on research projects and funding

resources

The main obstacle of external projects is co-financing by the resources from the

Institute. This policy is based on comfort financing of the research Institutes

which makes real problems in our conditions.

92

5. Organisation of PhD studies, other pedagogical activities

i. List of accredited programmes of doctoral studies (as stipulated in the

previously effective legislation as well as in the recently amended Act on the

Universities)

Previously effective legislation:Normal and pathological physiologyPharmacologyAnimal PhysiologyBiochemistry

Recent legislation:Normal and pathological physiologyPharmacologyAnimal PhysiologyBiochemistry

ii. Summary table on doctoral studies (number of internal/external PhD students;

number of students who completed their study by a successful thesis defence;

number of PhD students who quitted the programme)

PhD study

number of potential PhD supervisors

PhD students

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sis

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internal 13 4 12 3 2 9 1 2 12 3

external 4 5 5 3 4 1

supervised at external institution by the research employees of the assessed organisation

1 2

31.12.200531.12.2003 31.12.2004 31.12.2006

20 20 20 20

iii. Postdoctoral positions supported by

a) external funding (specify the source)

External funding:Dr. S. Wein – European Commission, project of Centre of Excellence, 2003Dr. I. Bodnar - European Commission, project of Centre of Excellence, 2003Dr. S. Mostbock - European Commission, project of Centre of Excellence, 2003

93

b)

c) internal funding - the Slovak Academy of Sciences Supporting Fund of Stefan

Schwarz

Internal funding:Mgr. D. Macejová – 2004MUDr. R. Dunčko – 2004Mgr. F. Monček – 2005MUDr. B. Mravec – 2005Mgr. L. Kubovčáková – 2006

iv. Summary table on pedagogical activities in undergraduate programmes for

each year

Teaching 2003 2004 2005 2006

lectures (hours/year) 62 73 67 75

practicum courses (hours/year) 1435 946 308 1252

supervised diploma works (in total) 10 5 2 8

members in PhD committees (in total) 6 6 12 12

members in DrSc. committees (in total) 5 6 6 6

members in university/faculty councils (in total)

1 2 2

members in habilitation/inauguration committees (in total)

3 2 3 3

v. List of published university textbooks

General and Clinical Endocrinology (A. Kreze, P. Langer, I. Klimeš, L. Stárka, J. Payer, J. Michálek, eds.), AEP, Bratislava, 2004, pp. 1-910

Rheumathology in Theory and in Practice VI, Osveta, Martin, 2004 (1 chapter)

Interaction of Drugs in Clinical Practice, L. Magulová, L. Božeková, M. Kriška (eds.), Slovak Academic Press, Bratislava, 2003 (1 chapter)

Memorix of Clinical Pharmacology and Drugs, M. Kriška et al.., SAP, Bratislava, 2006 (6 chapters)

In the year 2004, post gradual textbook Basic and Clinical Endocrinology has been published. Two of the several editors are represented by two leading researchers of our Institute, and other researchers of the Institute contributed to completion of 19 chapters.

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The BCE is used as a main textbook for taking the specialization board in clinical endocrinology in our country.

vi. Number of published academic course books

none

vii.List of joint research laboratories/facilities with the universities

Centre of Excellence of the Slovak Academy of Sciences (CENDO) with Slovak Medical

University and Faculty of Natural Sciences of the Comenius University in Bratislava was

established in 2006.

viii. Supplementary information and/or comments on doctoral studies and

pedagogical activities

The Institute of Experimental Endocrinology has been selected a suitable place to teach the PhD students and young scientists at the European level, as demonstrated by offering PhD and postdoctoral positions within the project of Centre of Excellence supported by EC. Based on scientific results obtained in this project and education process at our Institute, a Greek physician, A. Makatsori, M.D., obtained her PhD degree in pharmacology in 2004. At the time of getting the PhD degree, almost all PhD students graduating in the period 2003-2006 were authors or co-authors of scientific publications in journals with high impact factor. Many of them have been accepted for postdoctoral positions in top laboratories of medical research in the USA or Europe.

The Institute is approved to lead PhD studies in 4 study disciplines and several scientists are the members or even the leaders of the committees for PhD or DSc. Degree. The positive relation between the Institute and universities is documented by a high number of researchers selected as members of several PhD committees created at individual universities according to the new legislation. Senior scientists of the Institute perform also high quality pregraduate teaching, mainly in pharmacology, physiology and genetics. The quality of teaching and science at the Institute is demonstrated also by inauguration of two full professors of the Medical Faculty of Comenius University. One senior scientist of the Institute is leading the Department of Physiology at the Slovak Health University.

6. Direct output to the society

(applications of results, popularisation and outreach activities)

i.List of the most important results of applied research projects

[1] Mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic beta cell KATP

channel have recently been shown to be the most common cause of permanent neonatal diabetes mellitus (PNDM). Investigation of PNDM patients in the Slovak Children Diabetes Registry was performed. In insulin treated patients who matched the clinical criteria for PNDM, the KCNJ11 or ABCC8 genes were sequenced, and mutation carriers were invited for transfer to sulphonylurea. Eight patients with diabetes onset before the 6th month of life without remission were identified. With a mean of 71,805 live births per year since 1981, the PNDM incidence in Slovakia is approximately one case in 215,417 live births before the 6th month. One of the

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patients identified had died, and one has Wolcott-Rallison syndrome. In four patients, 3 different KCNJ11 mutations were found (two cases with R201H, and two novel mutations H46Y and L164P). Three patients with the KCNJ11 mutations R201H and H46Y were transferred from insulin to sulphonylurea, decreasing their HbA1c from 9.3-11.0% on insulin to 5.7-6.6% on sulphonylurea treatment. One patient has a novel V86A mutation in the ABCC8 gene, and was also successfully transferred to sulphonylurea. The data obtained are the first classical example of pharmacogenetics in diabetology, since the genetics cause of the insulin deficiency determines the response to treatment. These results have been generated within a long-term international collaboration with the Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, UK. The data has been published also in a prestigious journal with the top third impact factor in biomedicine at all.

[2] Screening of various forms of monogenic diabetes as well as establishment and management of the DNA repository in Slovakia. Studies of monogenic forms of diabetes, mutations and polymorphisms in the HNF1-alpha gene, which is responsible for the MODY3 subtype unveiled in 31 (18M/13F) probands and their 80 blood related family members that in six probands and their 11 blood relatives five different mutations were identified: R131Q and Y163N on exon 2, R200Q and R229P on exon 3, and R263C on exon 4. In 98 investigated subjects several polymorphisms - on exon 1 (L17L, A98V, I27L), exon 4 (G288G), exon 7 (L459L, S487N) and exon 8 (T515T) were identified. The data obtained indicates that 19% of all probands with clinical suspicion for MODY3 carries indeed a defect of the HNF1-alpha gene. This first information on appearance of MODY3 in Slovakia will be gradually re-evaluated via incorporating new DNA analysis data originating from appropriate patients identified within the screening program (2004).

[3] Analysis of mRNA for enzymes synthesizing catecholamines in adrenal gland medullar tumours showed high expression of TH and DBH genes, but low concentration of mRNA for PNMT, an enzyme synthesizing adrenalin. Applying this analytical method will help to diagnose the presence of pheochromocytoma. Low molecular weight proteomic analysis helps to identify patients endangered by metastatic form of pheochromocytoma. This is result of international collaboration with significant Slovak contribution (Brouwers FM, Petricoin EF, Ksinantova L, Breza J, Rajapakse V, Ross S, Johann D, Mannelli M, Shulkin BL, Kvetnansky R, Eisenhofer G, Walther MM, Hitt BA, Conrads TP, Veenstra D, Mannion DP, Wall MR, Wolfe GM, Fusaro VA, Liotta LA, Pacak K: Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma. ENDOCRINE-RELATED CANCER 12: 263-272, 2005, IF = 4,597 (2004). This improvement of diagnostics was discussed in the editorial article of the NATURE CLINICAL PRACTICE ONCOLOGY 9 (2): 439-440, 2005 (Rebeca Orreland: Novel method for distinguishing metastatic and benign pheochromocytoma).

[4] As a result of increased caloric intake or growth hormone deficiency (GHD) specific central obesity may develop as a main feature of the metabolic syndrome. It is associated with activation of signaling pathways related to cell stress and inflammation. The studies of molecular mechanisms of the role of chronic inflammation in the adipose tissue of clinically healthy, but obese young men, as well as of overweight young patients with verified growth hormone deficiency in adulthood were performed. The total amount of subcutaneous and visceral fat (as measured by magnetic resonance imaging) was increased in subjects with simple obesity. GHD patients had higher waist circumferences due to an increase of subcutaneous adipose tissue when compared to their BMI, age and sex-matched controls without GHD. The hsCRP levels (marker of inflammation) were significantly higher both in the obese

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subjects and in GHD patients when compared to their own controls, suggesting the presence of inflammation in both groups studied. Moreover, the mRNA levels for CD68 and CD14 (markers of macrophage activity) and proinflammatory adipokines (TNFa, IL-6, PAI-1) were higher in fasting state or during euglycemic hyperinsulinemia. Finally, gene expression for proinflammatory parameters studied showed a continual increase over a range of the subcutaneous adipose tissue mass, both in obese clinically healthy subjects and in patients with GHD. The presence of inflammation in the adipose tissue of obese subjects was confirmed also by results of the high-throughput protein array (measurement of 120 proteins in 1 sample of adipose tissue) study. Using this technology, it was found in the obese group that 27 proteins are presented at higher levels. Among these proteins there were leptin, growth factors and their receptors, number of chemokines, cytokines and their receptors, and other receptors and enzymes. For selected cytokines results obtained with protein array were compared with mRNA levels in the same tissue as measured using the real-time PCR. This is the first evidence on molecular mechanisms of chronic inflammation in the adipose tissue of clinically healthy (but with "molecular" disease) obese young men, which may participate in the development of insulin resistance. Chronic inflammation at the adipose tissue level is present also in patients with GHD, where elevated accumulation of central fat together with an insufficient insulin secretion during oGTT seem to contribute to an impairment of glucose tolerance seen in the GHD subjects. A part of this data has been accepted for publication in the Obesity Research in US (IF 3.9)

[5] Based on the complex endocrine picture of patients with rheumatoid arthritis concept of dehydroepiandrosterone supplementation in the therapy of rheumatoid arthritis was supported. Implementation of the obtained results in clinical monitoring and therapy is maintained by National Institute of Rheumatic Diseases, Piestany. (2003).

[6] In contrast to the traditional view, it was shown that the secretion of stress hormones in persons with high trait anxiety may be too low and that increased levels of some stress hormones during stress situations contribute to better coping with stress. It was found that plasma levels of cortisol, adrenaline and noradrenaline during stress were lower in the group of anxious subjects. Increased neuroendocrine activity during stress was induced by administration of selected amino acids (lysine, arginin) used as food additives. The results suggest an anxiolytic action of these amino acids. Subjects with better cognitive performance in another model of mental stress had significantly higher cortisol levels compared to those in persons with worse performance. Higher adrenaline and noradrenaline levels correlated with higher occurrence of mistakes, i.e. with worse cognitive performance during stress. Further studies revealed that high trait anxiety does not result in global hypo- or hyper-responsiveness, but in complex alterations in the coordination of neuroendocrine system in response to stressors. Correlation analysis in anxious subjects showed that lower adrenocorticotropin (ACTH) and cortisol responses during stress were associated with exaggerated perception of stress and depression feelings. This relationships were absent in low anxiety subjects. Obtained results allow suggesting that an adequate concentration of cortisol is needed for optimal emotional and cognitive coping with stress.

List of the most important studies commissioned for the decision-making authorities, the government and NGOs, international and foreign organisations

[1] Report on space activities in Slovak republic for the Permanent mission of SR at United Nations – Committee COPUOS. (RNDr. R. Kvetňanský, DrSc., and MUDr. L. Macho, DrSc.)

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[2] Participation at the elaboration of “Conception of state policy in the field of research and utilization of space” for The Council for science and technique of the Government of SR

[3] Elaboration of responses for the Questionnaire from EC, explaining Slovak opinion at the meeting of Space Council held on November 25, 2004 in Brussels.

ii. List of the most important popularisation activities

IN ELECTRONIC MEDIA

2003

Assoc. Prof. PharmDr. D. Ježová, DrSc.:

SLOVAK RADIO DEVIN – 13. and 15.01 2003 interview, topic: Stress and culture. SLOVAK RADIO – 24.04.2003: discussion about animal protection and relation to

medical research. SLOVAK RADIO – 05.09.2003: discussion on the topic STRESS SLOVAK TELEVISION STV1, 12.04.2003: discussion about research work

RNDr. R. Kvetňanský, DrSc. SLOVAK RADIO – 26.06.2003: discussion about research topics at the Institute and

the importance of Centre of excellence SLOVAK RADIO – 05.10.2003: discussion program on the topic STRESS TV STATION MARKIZA - 20.02.2003: The 4th anniversary of Slovak astronaut

flight, an interview TV STATION MARKIZA – 02.08.2003: reportage on 8th Symposium on

Catecholamines and Other Neurotransmitters in stress, Smolenice 26.06.-03.07.2003

Ing. E. Šeböková, DrSc. SLOVAK RADIO – 04.12.2003: discussion on Obesity as the global problem

2004MUDr. V. Štrbák, DrSc. SLOVAK RADIO – 26.01.2004: discussion on the research activities of Institute of

Experimental Endocrinology SLOVAK RADIO – 07.11.2004: interview on research funding

Assoc. Prof. PharmDr. D. Ježová, DrSc. TV STATION TA3 – 09.11.2005: interview on the research of stress and

depression, an international broadcasting in German language

2005RNDr. R. Kvetňanský, DrSc. TV STATION TA3 – 10.10.2005: interview on the opening micro Pet laboratory

(positron tomography) for small laboratory animals

MUDr. V. Štrbák, DrSc. SLOVAK RADIO REGINA – 13.12.2005: discussion about the visit of USA

ambassador at the medical institutes of Slovak Academy of Sciences

2006Prof. PharmDr. D. Ježová, DrSc.

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TV STATION TA3 – 20., 21. and 22.08.2006: discussion about personal research work, research activities and practical impact of results to manage stress, depression, prophylaxis and therapy of psychiatric disorders

SLOVAK RADIO – 04.07.2006: discussion program How to manage stress human health and about research of stress

Prof. MUDr. I. Klimeš, DrSc. TV STATION STV1 – 23.08.2006: discussion on the discovery, that the therapy

of some types of neonatal diabetes with gene mutation can be treated by sulphonylurea tablets instead of insulin

TV STATION TA3 – 23.08.2006: interview on the discovery of new diagnosis and treatment of neonatal diabetes without insulin

SLOVAK RADIO – 31.08.2006: interview about molecular biology methods for converting insulin therapy for sulphonylurea derivatives tablets

RNDr. R. Kvetňanský, DrSc. SLOVAK RADIO – 01.03.2006: discussion on subject STRESS: what is stress ,

what kind of processes characterize stress, what is stressor and stress reaction

MUDr. P. Langer, DrSc. SLOVAK RADIO – 20.08.2006: The talk about the research work acknowledge

by Slovak Academy of Sciences award

PRINTED MEDIA

2003Assoc. Prof. PharmDr. D. Ježová, DrSc. With science we are in EU. Quark 1: 6/7, 2003 We need stress too much of stress is harmful. Pravda XIII/112, 17.05.2003 Stress life of tested volunteer On the wings of uniqueness. TV complete, no. 17, 2003 Eight wings uplifted Slovakia. Slovenka, No. 16, 2003 Crystal wing to celebrities. Economic newsletter Crystal wing awards. SME newspaper No.87, 14.04.2003 Extraordinary persons were awarded by Crystal wing. Novy čas newsletter,

14.04.2003

RNDr. R. Kvetňanský, DrSc. The science in Bohemia and in Slovakia. Lidove noviny newspaper, 04.01.2003

2004Assoc. Prof. PharmDr. D. Ježová, DrSc. European excellence. Vecernik newspaper No. 161, 19.08.2004

MUDr. V. Štrbák, DrSc. Two meters are standard. Format, weekly newspaper, 27.9.2004

2005Ing. J. Brtko, DrSc. Anxieties of scientists community on toxic chemicals in environment. Spravy SAV,

No. 11, 2005

RNDr. M. Fickova, CSc.

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Endocrine disruptors devastate our health. Quark No. 6, 18-20, 2005

Ing. Š. Zorad, CSc. Report from The Czech and Slovak National Peptide Conference, The European

Peptide Society Newsletter 33: 6-7, 2005

RNDr. R. Kvetňanský, DrSc. The sign of stress. TELEplus, No. 25, 03.12.2005

2006Prof. PharmDr. D. Ježová, DrSc. Why boys do not have breasts and girls do not have moustache. Newspaper Pravda

XVI/192, 19.08.2006 Who is not killed by stress is strengthened. Pravda XVI/237, 14.10.2006 Our fellow stress. TELEplus, No.22, 2006 The work could devastate you. Economic newspaper No.200, p. 21, 2006 There is no vaccine against stress. Bajecna zena No.50, p. 23, 2006

Prof. MUDr. I. Klimeš, DrSc. Diabetes of neonatal could be treated with tabletes. SITA 23.08.2006 Interview on treatment of diabetes. Zdravotnicke noviny No. 33, 14.09.2006 Milestone in diabetes history in the presence of Slovakia. Zdravotnicke noviny No.32,

2006 (07.09.2006) From insulin therapy to sulphonylurea therapy. Kazuistika v diabetologii No.3, 2006 Further key for diabetes cognition. Spravy SAV No.9, 2006 New way in the treatment of diabetes mellitus. Molekularna medicina No.10, 2006 Neonatal diabetes is treated by tablets. Kauzistiky v diabetologii No.4, 2006

MUDr. P. Langer, DrSc. Hot spot bellow Strazske. Discussion about the cooperation with universities and

environmetal pollution. Quark No.10, 2006 Extraordinary editorial activity of IEE SAS. Spravy SAV No2, 2006 Promising light for sad priority. Spravy SAV, No7-8, 2006 Suspicious connections between chemicals and diabetes. Diabetik No.5, 2006

RNDr. R. Kvetňanský, DrSc. PRAVDA newspaper, Slovak research is interesting in moon flights, an interview.

07.12.2006 The most dangerous is psychological stress. Euroreport plus, p. 46-47, 2006

MUDr. V. Štrbák, DrSc. The project which has changed to nightmare. Forum scientiae et sapientiae, Veda

XIII(3) : 24-25, 2006

Press conferences Opening of the microPet laboratory. 10.10.2005 (MUDr. V. Štrbák, DrSc. and RNDr.

R. Kvetňanský, DrSc.) DNA diagnosis of neonatal diabetes enables accurate treatment. UP SAV 23.08.2006

(prof. MUDr. I. Klimeš, DrSc.) Press conference on the occasion of SAV award for the cooperation with universities.

UP SAV, 22.06.2006 (MUDr. Panger,DrSc.)

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Educative courses Educative course: „Neurotransmitters and Hormones“, IEE SAS and Faculty of

medicine of Comenius University, Bratislava, October 24 – November 14, 2005 (D. Jezova, 4 lectures).

Educative course: „How the stress research is performed in Bratislava and how in abroad? By the same way! Come to see it!” IEE SAS, November 8, 2005 (D. Jezova, 1 lecture).

Educative course: „Neuroanatomical techniques in the process of exploration of the brain which are usable in the revealing process of stress response to stress“ Part I. Imunohistochemistry, IEE SAS, December 15, 2005 (A. Kiss, 1 lecture).

Educative course for talented students of Bratislava's elementary schools, IEE SAS, November 29, 2006 (D. Jezova, 1 lecture).

Internet popularization - Prof. MUDr. Iwar Klimeš,DrSc.

Neonatal diabetes can be treated by tablets www.fitserver.sk, 23.08.2006

Neonatal diabetes …www.24hod.sk, 23.08.2006

Neonatal diabetes.... www.exil.sk/site/spravy, 23.08.2006

Neonatal diabetes.... www.aktuality.sk/forum/prispevky, 23.08.2006

Neonatal diabetes.... www.searchserver.sk, 23.08.2006

Neonatal diabetes.... www.dia.sk, 23.08.2006

Neonatal diabetes.... www.denne.sk, 23.08.2006

Neonatal diabetes.... http:// netnoviny.sk

Neonatal diabetes.... www.oblubene.sk

Neonatal diabetes.... www.citaj.sk

Neonatal diabetes.... www.zoznam.sk

Neonatal diabetes.... www.hladam.sk

Neonatal diabetes.... www.mednews.sk

Neonatal diabetes.... http:// proba.preson.sk 23.08.2006 (Prešov online)

Neonatal diabetes… www.koson.sk (webnews) 23.08.2006

iii. List of patents issued abroad, incl. revenues

none

iv. List of the patents issued in Slovakia, incl. revenues

none

v. List of licences sold abroad, incl. revenues

none

vi. List of licences sold in Slovakia, incl. revenues

none

vii. List of contracts with industrial or other partners, incl. revenues

[1] The joint laboratory DIABGENE of The Laboratory of Diabetes and Nutrition (IEE SAS, Bratislava, Prof. MUDr. I. Klimeš, DrSc.) and Children Department of

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National Institute of Endocrinology and Diabetes in Ľubochna (Assoc. Prof.MUDr. J. Michálek, CSc.) No revenues

[2] The contract between IEE SAS (MUDr. R. Imrich, PhD., MUDr. M. Vigaš, DrSc.) and National Institute of Rheumatoid Diseases in Piešťany (prof. MUDr. J. Rovensky, DrSC) No revenues

[3] The contract between IEE SAS and BIONT company for the utilization of microPet camera. No revenues

List of research projects with industrial or other partners, incl. revenues

[1] National diabetes program: Screening of DM-2, MODY-3 and MIDD (Assoc. Prof. MUDr. Iwar Klimeš, DrSc., IEE SAS) and National Institute of Endocrinology and Diabetes, Ľubochňa (Assoc. Prof. MUDr. J. Michálek, CSc., Ministry of Health SR). No revenues

[2] The effect of chronic inflammation on metabolism in rheumatic diseases. IEE SAS (MUDr. Milan Vigaš, DrSc.) and Ministry of Health SR, National institute of rheumatoid diseases, (prof. MUDr. Jozef Rovenský, DrSc., Ministry of Health SR) No revenues

[3] Joint project of IEE SAS (RNDr. R. Kvetňanský, DrSc.) and Cyclotron centre SR (Prof. J. Ružička, DrSc.) and NIH, USA. No revenues

[4] Cytotoxic and apoptotic properties of secondary metabolites from selected plants. IEE SAS (RNDr. M. Fickova, CSc.) and The Faculty of Pharmacy UC (prof. D. Grancai, CSc., Ministry of Education SR). No revenues

viii. Summary of outreach activities

Outreach activities 2003 2004 2005 2006 total

studies for the decision sphere, government and NGOs, international and foreign organisations 2 3 3 1 9

articles in press media/internet popularising results of science, in particular those achieved by the Organization

12 2 10 38 62

appearances in telecommunication media popularising results of science, in particular those achieved by the Organization

11 3 3 8 25

public popularisation lectures 6 1 7

ix. Supplementary information and/or comments on applications and

popularisation activities

Increased popularization activities are based on awareness of importance of the scientists of Society information about the research outcome. One European Social Fund project is specifically devoted to educational and popularization activities. With time cooperation of public media and their approach significantly improved.

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7. Background and management. Staffing policy and implementation of

findings from previous assessments

i. Summary table of personnel

Personnel 2003 2004 2005 2006

all personel 76 76 84 85

research employees from Tab. Research staff

39 39 40 39

FTE from Tab. Research staff 36,75 37,28 37,63 36,89

averaged age of research employees w ith university degree

48,25 42,57 45,29 45,24

ii. Professional qualification structure

Number of 2003 2004 2005 2006

DrSc. 12 12 12 10

PhD / CSc. 19 18 22 23

Prof. 1 2

Doc./Assoc. Prof. 3 3 3 2

iii. Status and development of research infrastructure incl. experimental,

computing and technical base (description of the present infrastructure,

premises, and material and technical resources. Infrastructure, instrumentation

and major technical equipment necessary for the achievement of the objectives

specified in the research Concept)

Despite marginal support of science in Slovakia some laboratories of the Institute were able to introduce top methodology and equipment. Nevertheless even basal running of the Institute depends on the significant support from all projects. Comparison with neighbouring countries reveals remarkable disadvantageous situation in Slovakia.

iv. Status and development of bibliographic resources, activities of the

Organisation’s library and/or information centre

The Library of IEE besides services according with leadings of journals and books of its book funds affords also services including recherché, citations, collecting basic information – about publishing activities of the scientists if the Institute.

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v. Describe how the results and suggestions of the previous assessment were

taken into account

No suggestions were received.

vi. Supplementary information and/or comments on management, research

infrastructure, and trends in personnel development

Each Ph.D. student after graduation is offered permanent position at the Institute. Most of them are sent to cooperating laboratories abroad for sabbatical stay, they return only exceptionally at present.

Other information relevant to the assessment

Here are several points which would be helpful if solved:

Better support of research would enable scientists to improve equipment, to co-finance projects from external resources, to attract young scientists to stay or even to return from abroad. Education of Ph.D. students is rather complicated and needs reform: it fully depends on the good will of colleagues at Universities.

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